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Simple Summary: Adult-type diffuse gliomas are the most common primary brain tumours. Radiotherapy is one of the therapeutic options offered upfront and/or after surgery both in naïve and recurrent patients. Magnetic resonance imaging (MRI) is the recommended technique for treatment response evaluation and follow-up. However, in patients previously treated with radiotherapy, MRI might be difficult to interpret since recurrent disease and treatment-related changes often appear similar. Therefore, other imaging modalities, including positron emission tomography (PET), have been explored in this clinical setting. The present work focused on PET imaging in adult-type diffuse gliomas aims to review available literature data and assess the capability of PET in discriminating between radiation necrosis and disease relapse in irradiated patients. Adult-type diffuse gliomas are treated with a multimodality treatment approach that includes radiotherapy both in the primary setting, and in the case of progressive or recurrent disease. Radiation necrosis represents a major complication of radiotherapy. Recurrent disease and treatment-related changes are often indistinguishable using conventional imaging methods. The present systematic review aims at assessing the diagnostic role of PET imaging using different radiopharmaceuticals in differentiating radiation necrosis and disease relapse in irradiated adult-type diffuse gliomas. We conducted a comprehensive literature search using the PubMed/MEDLINE and EMBASE databases for original research studies of interest. In total, 436 articles were assessed for eligibility. Ten original papers, published between 2014 and 2022, were selected. Four articles focused on [18F]FDG, seven on amino acid tracers ([18F]FET n = 3 and [11C]MET n = 4), one on [11C]CHO, and one on [68Ga]Ga-PSMA. Visual assessment, semi-quantitative methods, and radiomics were applied for image analysis. Furthermore, 2/10 papers were comparative studies investigating different radiopharmaceuticals. The present review, the first one on the topic in light of the new 2021 CNS WHO classification, highlighted the usefulness of PET imaging in distinguishing radiation necrosis and tumour recurrence, but revealed high heterogeneity among studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancers (NSCLCs) can be treated with chemotherapy, radiotherapy, immunotherapy, or a combination before undergoing surgical resection. However, uncertainty remains regarding the overall outcomes of patients undergoing minimally invasive surgical (MIS) resection of the lung, following systemic treatment. As such, we studied the existing data on outcomes of this patient population via a comprehensive dive into the literature and performed a meta-analysis. Our findings indicate that MIS can be safely performed following systemic treatment in patients with NSCLC. Notably, MIS resection offers added benefits including significantly higher lymph node yield compared to open surgery. We also address the various complication rates of both open and MIS surgical approaches, underscoring the importance of surgeon preparedness to convert MIS approaches to open surgeries in precarious circumstances. Overall, this study provides valuable insights into the safety and efficacy of MIS resection post-systemic treatment for patients with NSCLC, offering potential improvements in patient outcomes and guidance to surgical decision making. Background: Minimally invasive surgeries for non-small cell lung cancers (NSCLCs) such as video-assisted thoracoscopic surgeries (VATSs) and robotic-assisted thoracoscopic surgeries (RATSs) have become standard of care for patients needing surgical resection in early stages. The role for neoadjuvant systemic therapy has increased with patients receiving neoadjuvant systemic chemotherapy and immunotherapy. However, there has been some equipoise over the intraoperative and overall outcomes for these patients. Here, we review the current data regarding outcomes of patients undergoing minimally invasive thoracic surgical resection after systemic chemotherapy, immunotherapy, or both. Methods: A systematic literature review of randomized controlled trials and observational studies presenting data on patients with NSCLC that underwent neoadjuvant systemic therapy followed by minimally invasive surgery was performed assessing complications, conversion rates, and lymph node yield. Results: Our search strategy and review of references resulted in 239 publications to screen with 88 full texts assessed and 21 studies included in our final review. VATS had a statistically significant higher lymph node yield in five studies. The reported conversion rates ranged from 0 to 54%. Dense adhesions, bleeding, and difficult anatomy were the most common reported reasons for conversion to open surgeries. The most common complications between both groups were prolonged air leak, arrhythmia, and pneumonia. VATS was found to have significantly fewer complications in three papers. Conclusions: The current literature supports VATS as safe and feasible for patients with NSCLC after neoadjuvant systemic treatment. Surgeons should remain prepared to convert to open surgeries in those patients with dense adhesions and bleeding risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Neo-adjuvant systemic (NAS) therapy for melanoma is leading the way in immunotherapy for oncology. There is both a strong biological rationale to support NAS therapy, as well as exciting results in terms of superior efficacy to the current standards of care. Simply giving pembrolizumab 3 doses prior to surgery and 14 after rather than all 17 courses as adjuvant therapy only, demonstrated a 23% improvement in event-free survival (EFS). Combination immunotherapy with ipilimumab and nivolumab seems even more potent with ~60% of patients achieving Major Pathologic Responses (MPR) vs. ~25–30% for single agent anti-PD-1. NAS therapy will allow for a tailored approach to the therapy of melanoma patients, which includes a potential safe de-escalation of the extent of surgery and discontinuation of systemic therapy for MPR patients. And early identification of non-responders who can be directed towards clinical trials with novel therapies. These developments are now splashing over to other solid tumors, but there is still a need to develop a bespoke panel of biomarkers to further improve upon the current treatments. NAS therapy will soon become the novel standard of care approach for macroscopic stage III melanoma. Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient's immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy. Another benefit of NAS therapy potentially includes identifying patients who have a favorable response, which could offer an opportunity for the de-escalation of the extent of surgery and the need for adjuvant radiotherapy and/or adjuvant systemic therapy, as well as tailoring the follow-up in terms of the frequency of visits and cross-sectional imaging. In this paper, we will review the rationale for NAS therapy in resectable metastatic melanoma and the results obtained so far, both for immunotherapy and for BRAF/MEKi therapy, and discuss the response assessment and interpretation, toxicity and surgical considerations. All the trials that have been reported up to now have been investigator-initiated phase I/II trials with either single-agent anti-PD-1, combination anti-CTLA-4 and anti-PD-1 or BRAF/MEK inhibition. The results have been good but are especially encouraging for immunotherapies, showing high durable recurrence-free survival rates. Combination immunotherapy seems superior, with a higher rate of pathologic responses, particularly in patients with a major pathologic response (MPR = pathologic complete response [pCR] + near-pCR [max 10% viable tumor cells]) of 60% vs. 25–30%. The SWOG S1801 trial has recently shown a 23% improvement in event-free survival (EFS) after 2 years for pembrolizumab when giving 3 doses as NAS therapy and 15 as adjuvant versus 18 as adjuvant only. The community is keen to see the first results (expected in 2024) of the phase 3 NADINA trial (NCT04949113), which randomized patients between surgery + adjuvant anti-PD-1 and two NAS therapy courses of a combination of ipilimumab + nivolumab, followed by surgery and a response-driven adjuvant regimen or follow-up. We are on the eve of neo-adjuvant systemic (NAS) therapy, particularly immunotherapy, becoming the novel standard of care for macroscopic stage III melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Undifferentiated embryonal sarcoma of the liver is a rare pediatric tumor with a traditionally poor prognosis. Dual treatment with a combination of surgery and chemotherapy has produced much improved outcomes. The sharing and consolidation of various case series and clinical experiences allow for the prompt design of appropriate treatment advice. Even in the event of unresectable or recurrent diseases, other treatment modalities such as orthotopic liver transplantation and radiotherapy can be offered. This review of treatment recommendations for rare undifferentiated embryonal sarcoma of the liver has important clinical use. Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal tumor with a highly malignant potential. It occurs almost exclusively in the pediatric population and typically has a poor outcome. Although previous studies have reported dismal prognoses, recent advances in combined treatment modalities, e.g., surgery and chemotherapy, have given cause for optimism. Even in those diseases not amenable to complete surgical resection or refractory diseases, other treatment modalities, such as liver transplant, have yielded promising results. This paper provides a review of the current treatment modalities for hepatic undifferentiated embryonal sarcoma in children. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiolabeled choline and PSMA PET have been largely tested in the initial staging of prostate cancer and for biochemical recurrence. Moreover, diverse data are now available about their role in the evaluation of response to local and systematic therapies, and their predictive impact on the prognosis, before and after therapy. Therefore, in the present systematic review, we aimed to describe the available data, to summarize the current evidence in these settings of disease. The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the "Quality Assessment of Prognostic Accuracy Studies" tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [68Ga]PSMA-11 (16 articles/1123 patients) or [11C]/[18F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [68Ga]PSMA-11, three with [11C]Choline, one with [18F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [18F]Choline PET/CT (n = 121 patients) and three with [68Ga]PSMA-11 PET (n = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [18F]Choline and [68Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [68Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a feasible method of intraperitoneal drug administration in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3–4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61–0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our study is to provide a wide perspective on the available literature data on the immune landscape of breast cancers, focusing on TILs and PD-L1 expression across different breast cancer subtypes. Moreover, treatment options such as immunotherapy and chemotherapy in adjuvant and neoadjuvant settings are discussed, along with the most relevant cut-offs and scores for TILs and PD-L1 pathological assessment. With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0–10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting. [ABSTRACT FROM AUTHOR]

Simple Summary: Physical function is important for older people to maintain selfcare and independence. Physical function may decline during oncologic therapy. In this study, a program to help maintain physical function was developed and tested. Cancer patients, 60 years and older, starting outpatient radiotherapy participated. The individual health condition, risk factors and quality of life were assessed. The results informed individual exercise plans and dietary recommendations. Participants received either paper-based or video-based instructions. After 12 weeks of intervention the assessments were repeated. Four weeks later, a questionnaire was sent to ask about physical activity, nutrition and quality of life. Twenty-four patients participated (14 women, 10 men) with a mean age of 70 ± 7 years. The majority rated the program as helpful. Paper-based or video-based instructions were appreciated equally. The intervention was feasible and showed potential benefit for the maintenance of physical function during outpatient radiotherapy and should be tested with a larger sample. Physical function (PF) in older patients with cancer may decline during and after oncologic therapy. This study aimed to develop and pilot test an individually tailored unsupervised physical activity (PA) program and dietary recommendations to promote PF in older patients with cancer. Following development and pretest, the intervention was pilot tested to explore feasibility, acceptance, adherence and potential benefit. Patients ≥60 years, with heterogeneous cancer diagnoses, starting outpatient radiotherapy were randomized in two study arms: paper-based vs. video-based instructions. Based on assessments of PF, PA, nutrition, cognition, mental health, social support, HRQOL and personal goals, participants received individual recommendations for PA and nutrition. After 12 weeks of intervention (T1), reassessments were performed. The postal 4-week follow-up questionnaire included PA, nutrition and HRQOL. Participants (n = 24, 14 female, mean age 70 ± 7 years) showed comparable characteristics in both study arms. The majority rated the program as helpful. Facilitators and barriers to PA adherence were collected. Both modes of instructions were appreciated equally. PF (EORTC QLQ-C30) declined slightly (not clinically relevant >10 pts.) at group level T0: 76 ± 16, T1: 68 ± 21, T2: 69 ± 24. The intervention was feasible, well accepted, showing potential benefit for the maintenance of PF during outpatient radiotherapy, and should be further tested in a larger sample. [ABSTRACT FROM AUTHOR]

Simple Summary: Many clinical trials have shown benefit for adding hyperthermia (heat) treatment to radiotherapy. Despite overall success, some patients do not derive maximum benefit from this combination treatment. Tumor hypoxia (low oxygen concentration) is a major cause for radiotherapy treatment resistance. In this paper, we examine the question of whether hyperthermia reduces hypoxia and, if so, whether reduction in hypoxia is associated with treatment outcome. The review is focused mainly on several clinical trials conducted in humans and companion dogs with cancer treated with hyperthermia and radiotherapy. Detailed measurements of temperature, hypoxia and perfusion were made and compared with treatment outcome. These analyses show that reoxygenation after hyperthermia occurs in patients and is related to treatment outcome. Further, reoxygenation is most likely caused by variable intra-tumoral temperatures that improve perfusion and reduce oxygen consumption rate. Directions for future research on this important issue are indicated. Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences tumor hypoxia, since hypoxia negatively influences radiotherapy and chemotherapy response as well as immune surveillance. Pre-clinically, it is well established that reoxygenation of tumors in response to HT is related to the time and temperature of exposure. In most pre-clinical studies, reoxygenation occurs only during or shortly after a HT treatment. If this were the case clinically, then it would be challenging to take advantage of HT induced reoxygenation. An important question, therefore, is whether HT induced reoxygenation occurs in the clinic that is of radiobiological significance. In this review, we will discuss the influence of thermal history on reoxygenation in both human and canine cancers treated with thermoradiotherapy. Results of several clinical series show that reoxygenation is observed and persists for 24–48 h after HT. Further, reoxygenation is associated with treatment outcome in thermoradiotherapy trials as assessed by: (1) a doubling of pathologic complete response (pCR) in human soft tissue sarcomas, (2) a 14 mmHg increase in pO2 of locally advanced breast cancers achieving a clinical response vs. a 9 mmHg decrease in pO2 of locally advanced breast cancers that did not respond and (3) a significant correlation between extent of reoxygenation (as assessed by pO2 probes and hypoxia marker drug immunohistochemistry) and duration of local tumor control in canine soft tissue sarcomas. The persistence of reoxygenation out to 24–48 h post HT is distinctly different from most reported rodent studies. In these clinical series, comparison of thermal data with physiologic response shows that within the same tumor, temperatures at the higher end of the temperature distribution likely kill cells, resulting in reduced oxygen consumption rate, while lower temperatures in the same tumor improve perfusion. However, reoxygenation does not occur in all subjects, leading to significant uncertainty about the thermal–physiologic relationship. This uncertainty stems from limited knowledge about the spatiotemporal characteristics of temperature and physiologic response. We conclude with recommendations for future research with emphasis on retrieving co-registered thermal and physiologic data before and after HT in order to begin to unravel complex thermophysiologic interactions that appear to occur with thermoradiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer remains one of the most dreaded cancers worldwide. The incidence of this relatively rare cancer is increasing by almost 1.0% per year. It is estimated that it will become the second leading cause of cancer-related mortality within the next 10 years. Despite the advances in oncology, radical resection, followed by adjuvant systemic chemotherapy, still offers the only realistic chance of curing this disease. Patient selection in specialized and high-volume centers improved perioperative morbidity and mortality rates over the last two decades. Additionally, due to improvements in both surgical techniques and systemic chemotherapy, the indications for resection are expanding to include more locally advanced cases. However, the role of neoadjuvant chemotherapy or radiotherapy remains unclear. This paper summarizes the data regarding current surgical management of pancreatic cancer and reviews future treatment prospects and the latest advances in perioperative strategies. Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Wilms tumor (WT) is a rare form of cancer that typically affects children and is usually confined to the kidneys. Extra-renal Wilms tumor (ERWT) is even rarer and develops in other areas of the body, such as the retroperitoneum and inguinal regions, and occasionally at the level of the spinal cord. We present a case report of a 4-year-old boy diagnosed with spinal ERWT, who was also affected with a spinal dysraphism. Our case-based systematic review of pediatric ERWT showed that a multimodal therapeutic approach (including surgery, chemotherapy, and radiotherapy) is important, but an international standardization of the staging approach and therapeutic protocols is needed to define the best clinical management in these children: indeed, there is a lack of clinical studies focused on pediatric ERWT and international trials are needed to achieve these objectives. Our research emphasizes the importance of timely diagnosis and treatment and, possibly, standardized medical approach, in order to improve the outcome of these very rare pediatric malignancies, whose clinical management is even more problematic in developing countries. Wilms Tumor (WT) is one of the most common renal tumors in the pediatric population. Occasionally, WT can primarily develop outside the kidneys (Extra-Renal Wilms Tumor, ERWT). Most pediatric ERWTs develop in the abdominal cavity and pelvis, whereas the occurrence of this tumor in other extra-renal sites represents a minor part of ERWT cases. In addition to describing a case of spinal ERWT (associated with spinal dysraphism) in a 4-year boy (to add a further clinical experience on this very rare pediatric tumor), we performed a case-based systematic literature review on pediatric ERWT. We retrieved 72 papers providing enough information on the diagnosis, treatment, and outcomes of 98 ERWT pediatric patients. Our research highlighted that a multimodal approach involving both chemotherapy and radiotherapy, after partial or complete tumor resection in most cases, was typically used, but there is no standardized therapeutic approach for this pediatric malignancy. However, this tumor may be potentially treated with a better success rate if the diagnostic confirmation is not delayed, the mass can be totally resected, and an appropriate and, possibly, tailored multimodal treatment can be promptly established. In this regard, an international agreement on a unique staging system for (pediatric) ERWT is definitely needed, as well as the development of international research, which may be able to gather several children diagnosed with ERWT and, possibly, lead to clinical trials which should also include developing countries. [ABSTRACT FROM AUTHOR]

Simple Summary: The introduction of new therapies for non-small cell lung cancer (NSCLC) has radically changed the point of view of thoracic surgeons, leading them to pay increasingly more attention not only to the clinical stage, but also to the genomic and molecular features of the disease and the potential for multimodality treatments. This is the concept of precision surgery in thoracic oncology. The aim of our paper is to summarize the changes in thoracic surgical practice that occurred after the introduction of immunotherapy and targeted therapy for the treatment of NSCLC. Non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. This is mostly because the majority of lung cancers are discovered in advanced stages. In the era of conventional chemotherapy, the prognosis of advanced NSCLC was grim. Important results have been reported in thoracic oncology since the discovery of new molecular alterations and of the role of the immune system. The advent of new therapies has radically changed the approach to lung cancer for a subset of patients with advanced NSCLC, and the concept of incurable disease is still changing. In this setting, surgery seems to have developed a role of rescue therapy for some patients. In precision surgery, the decision to perform surgical procedures is tailored to the individual patient; taking into consideration not only clinical stage, but also clinical and molecular features. Multimodality treatments incorporating surgery, immune checkpoint inhibitors, or targeted agents are feasible in high volume centers with good results in terms of pathologic response and patient morbidity. Thanks to a better understanding of tumor biology, precision thoracic surgery will facilitate optimal and individualized patient selection and treatment, with the goal of improving the outcomes of patients affected by NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Localized rectal cancer is currently managed with neoadjuvant therapy before surgery which includes concurrent chemoradiation therapy alone or a total neoadjuvant therapy approach which involves chemotherapy and concurrent chemoradiation sequentially. These strategies are changing, and optimal management of rectal cancer continues to evolve. Immunotherapy has entered the treatment paradigm in advanced rectal cancer for patients with microsatellite instability. A role for immunotherapy for early-stage disease has yet to be established. Clinical trials in rectal cancer incorporating immunotherapy in the neoadjuvant settings are underway however better understanding of the tumor microenvironment and targeting specific biomarkers may be more efficacious. In this paper, we report on rectal cancer tumor microenvironment changes following neoadjuvant chemoradiation. Identifying changes in biomarker expression within the tumor microenvironment may be predictive of better outcomes, improved response to immunotherapy and may also identify new targets which could lead to targeted therapeutic drug development. Background: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer. Methods: We accessed archival tissue from rectal cancer patients treated with neoadjuvant cCRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients. Results: We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant cCRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression. Conclusions: This provides a glimpse into the TME before and after neoadjuvant cCRT. We suggest that the biomarkers noted to be upregulated could be used for designing appropriate clinical trials and development of therapeutic targeted drug therapy in an effort to achieve better response to neoadjuvant therapy, increasing clinical and pathological complete response rates and improved overall outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Oesophageal adenocarcinoma (OAC) is a leading cause of cancer mortality in the United Kingdom with a 5-year survival rate of approximately 15%. Major contributors to poor outcome are late diagnosis and chemotherapy resistance, and while targeted therapies have benefitted certain cancer settings, they have had limited success in OAC. An understanding of the mechanisms mediating chemotherapy resistance could identify novel targets with the potential to improve standard treatments. This paper aimed to identify mediators of both OAC cancer cell pro-survival signalling and chemotherapy resistance, as well as determine potential small molecular compounds to counteract this. Gene set enrichment analysis of transcriptional data generated a gene-list with significant differential expression between responder and non-responder OAC patients. Gene functionality assessment using siRNA screening showed that targeting SRC had an anti-tumour effect in OAC cells with the potential to enhance chemotherapy treatment. In parallel to this, a compound screen showed the Src inihibitor dasatinib sensitised OAC cells to chemotherapy. Together, these findings suggest targeting SRC as a novel therapeutic strategy in OAC. Drug resistance limits the effectiveness of oesophageal adenocarcinoma (OAC) chemotherapies, leading to a poor prognosis for this disease. Elucidation of the underlying resistance mechanisms is key to enabling the identification of more effective treatments. This study, therefore, aims to identify novel therapeutic and/or chemotherapy sensitising drug targets in OAC. Transcriptional data from a cohort of 273 pre-treatment OAC biopsies, from patients who received neoadjuvant chemotherapy followed by surgical resection, were analysed using gene set enrichment analysis (GSEA) to determine differential gene expression between responding and non-responding OAC tumours. From this, 80 genes were selected for high-throughput siRNA screening in OAC cell lines with or without standard chemotherapy treatment. In parallel, cell viability assays were performed using a panel of FDA-approved drugs and combination index (CI) values were calculated to evaluate drug synergy with standard chemotherapy. Mechanisms of synergy were investigated using western blot, propidium iodide flow cytometry, and proliferation assays. Taken together, the screens identified that targeting Src, using either siRNA or the small molecule inhibitor dasatinib, enhanced the efficacy of chemotherapy in OAC cells. Further in vitro functional analysis confirmed Src inhibition to be synergistic with standard OAC chemotherapies, 5-fluorouracil (5-FU), and cisplatin (CDDP). In conclusion, a compound screen together with a functional genomic approach identified Src as a potential chemosensitising target in OAC, which could be assessed in a clinical study for poor prognosis OAC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: A combination of pertuzumab, trastuzumab, and chemotherapy is a standard treatment for patients with a type of breast cancer called HER2-positive. Before the BERENICE study, little was known about the safety and effectiveness of pertuzumab with trastuzumab after surgery. Cardiac safety was a particular concern, especially when the chemotherapy given before surgery included drugs called anthracyclines. BERENICE was designed to assess the cardiac safety of pertuzumab with trastuzumab before surgery in combination with two different types of anthracycline-based chemotherapies. This paper describes additional safety and effectiveness data from BERENICE after patients had undergone surgery and when they had finished treatment. The incidence of cardiac side effects was low regardless of anthracycline use. The cardiac safety of pertuzumab and trastuzumab is now well characterized based on our study and others. Available information supports the use of pertuzumab–trastuzumab-based therapies as a standard treatment in HER2-positive early breast cancer. BERENICE (NCT02132949) assessed the cardiac safety of the neoadjuvant–adjuvant pertuzumab–trastuzumab-based therapy for high-risk, HER2-positive early breast cancer (EBC). We describe key secondary objectives at final analysis. Eligible patients received dose-dense doxorubicin and cyclophosphamide q2w × 4 ➝ paclitaxel qw × 12 (Cohort A) or 5-fluorouracil, epirubicin, cyclophosphamide q3w × 4 ➝ docetaxel q3w × 4 (B) as per physician's choice. Pertuzumab–trastuzumab (q3w) was initiated from the taxane start and continued post-surgery to complete 1 year. Median follow-up: 64.5 months. There were no new cardiac issues and a low incidence of Class III/IV heart failure (Cohort B only: one patient (0.5%) in the adjuvant and treatment-free follow-up (TFFU) periods). Fourteen patients (7.7%) had LVEF declines of ≥10% points from baseline to <50% in Cohort A, as did 20 (10.5%) in B during the adjuvant period (12 (6.2%) in A and 7 (3.6%) in B during TFFU). The five-year event-free survival rates in Cohorts A and B were 90.8% (95% CI: 86.5, 95.2) and 89.2% (84.8, 93.6), respectively. The five-year overall survival rates were 96.1% (95% CI: 93.3, 98.9) and 93.8% (90.3, 97.2), respectively. The final analysis of BERENICE further supports pertuzumab–trastuzumab-based therapies as standard of care for high-risk, HER2-positive EBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Salvage lung resection for lung cancer is a relatively new concept, and most of the operated patients present non-small cell lung cancer (NSCLC). For small-cell lung cancer (SCLC), salvage surgery is extremely rarely performed, in highly selected patients proved with limited disease after radical chemoradiation, as an alternative to second-line chemotherapy. From the published cases, it appeared that salvation surgery for SCLC presents postoperative morbidity similar to salvage surgery for NSCLC, no postoperative mortality, and a median estimated overall survival of 92% at 2 years and 66% at 5 years. Salvage lung resection for SCLC may be a reasonable treatment in very highly selected patients, offering good local control and a favorable survival outcome. (1) Background: Salvation surgery for small-cell lung cancer (SCLC) is exceptionally performed, and only a few cases are published. (2) Methods: There are 6 publications that present 17 cases of salvation surgery for SCLC—the salvation surgery was performed in the context of modern clearly established protocols for SCLC and after including SCLC in the TNM (tumor, node, metastasis) staging in 2010. (3) Results: After a median follow-up of 29 months, the estimated overall survival (OS) was 86 months. The median estimated 2-year survival was 92%, and the median estimated 5-year survival was 66%. (4) Conclusion: Salvage surgery for SCLC is a relatively new and extremely uncommon concept and represents an alternative to second-line chemotherapy. It is valuable because it may offer a reasonable treatment for selected patients, good local control, and a favorable survival outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant therapy, used before surgery, is an important part of breast cancer treatment. Not only can it shrink tumors, but it can also provide valuable information on how the cancer responds to treatment, which can help physicians tailor further therapy. For aggressive types of breast cancer, such as HER2-positive and triple-negative breast cancers, targeted therapies and immunotherapy are often added to standard chemotherapy. Achieving a complete response to treatment (i.e., total absence of viable tumor from tissue removed during surgery) is usually a good sign, but it does not always mean better long-term outcomes for every patient. This review examines the evolution of neoadjuvant therapy in high-risk breast cancer and discusses recent clinical trials focused on optimizing treatment. It also highlights the need for new approaches to improve outcomes, especially for patients whose cancer does not fully respond to initial treatments. The use of neoadjuvant systemic therapy (NST) has become increasingly important in the treatment of breast cancer because of its various advantages. These include the ability to downstage tumors without compromising locoregional control and the potential to obtain valuable information about clinical and biological response to therapy with implications for individual prognoses. Surgical response assessment paves the way for response-adapted therapy, and pathological complete response (pCR; defined as ypT0/is ypN0) serves as an additional endpoint for drug development trials. Recommended NST regimens commonly consist of anthracyclines and taxane, with dose-dense anthracyclines and weekly paclitaxel often preferred, whenever feasible. For patients with human epidermal growth factor receptor-2 (HER2)-positive tumors, dual anti-HER2 therapy (trastuzumab and pertuzumab) is indicated together with NST in case of elevated risk of recurrence. For patients with triple-negative breast cancer (TNBC), adding carboplatin to NST correlates with improved pCR and survival rates, as does the addition of immune checkpoint inhibitors. For hormone receptor (HR)-positive/HER2-negative cancers, emerging data on NST including immune checkpoint inhibitors may elevate the significance of NST in high-risk luminal breast cancer. Here, we present a synthesis of the results from neoadjuvant clinical trials that aim at optimizing treatment options for patients with high-risk breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma (CM) is an aggressive skin cancer that develops from melanocytic cells. The most important prognostic factor is still the vertical tumour thickness according to Breslow. Liver function is associated with better overall patient outcomes and is currently under increasing investigation in cancer patients. Current findings show that liver function is an important factor in different tumour entities and represents a potential biomarker. Therefore, we aimed to evaluate liver metabolism by using liver scores in CM. High tumour thickness (≥1.66 mm) and aspartate transaminase-to-platelet ratio index (APRI ≥ 0.2241) at the initial diagnosis were associated with a worse prognosis in stage I and II melanoma. Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary treatment for operable pancreatic cancer involves surgery followed by adjuvant therapy, with an increasing use of perioperative or neoadjuvant chemotherapy. We performed a network meta-analysis to assess the comparative efficacy of various treatment approaches for resectable pancreatic cancer. A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone. Excluding Asian studies, the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen. The findings endorse the utilization of perioperative and multi-agent chemotherapy as the favored intervention for operable PC in Western nations. The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations. [ABSTRACT FROM AUTHOR]

Simple Summary: In-transit metastases (ITM) are a challenging aspect of advanced melanoma, traditionally treated with surgery. However, recent advances in systemic therapies, such as immune checkpoint inhibitors and targeted treatments, have significantly improved patient outcomes. These modern therapies are now often preferred over surgery alone. This article reviews the benefits of combining systemic and locoregional treatments, highlighting their potential to enhance survival and quality of life for patients with ITM. By integrating these approaches, we aim to provide a comprehensive strategy for optimizing melanoma treatment outcomes. In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma is the deadliest of all skin cancers. Therapy paradigms in cutaneous melanoma have changed significantly over the past 20 years, following both changes in the initial staging work-up of melanoma as well as in the available therapies. Regional recurrences after initial surgery are normally treated with nodal basin resection. However, some regional recurrences may present as bulky masses that can pose significant challenges in the treatment and control of the disease. It is well established that radiation therapy (RT) plays a role in locoregional control of malignancies in general. This review will attempt to discuss evidence for radiation therapy's role in reducing regional recurrence in the adjuvant setting in melanoma, identify adjuvant systemic therapy options, discuss systemic therapy–radiation therapy combinations, and identify paradigms and emerging evidence for the use of radiation therapy after neoadjuvant systemic therapy strategies are employed. In the landscape of Stage III locoregionally advanced cutaneous melanoma treatment, the post-immunotherapy era has sparked a number of questions on the management of the nodal basin. However, much of the available literature is not focused on radiation therapy as an adjuvant therapy. This literature review aims to illuminate the evidence surrounding radiation therapy's potential to mitigate regional recurrences in the adjuvant setting for melanoma. Additionally, it seeks to identify adjunct systemic therapy options and explore the synergy between systemic therapy and radiation. Despite strides in surgical techniques and systemic therapies, controlling regional Stage III melanoma remains a formidable clinical hurdle. While historical data strongly suggest the efficacy of adjuvant radiation therapy in reducing regional recurrence risk, its evaluation predates the advent of MAPK pathway inhibitors and robust immunotherapy options. Notably, clinical trials have yet to definitively demonstrate a survival advantage with adjuvant radiation therapy. Additional research should focus on refining the definition of high risk for regional recurrence through gene expression profiling or tumor immune profiling scores and elucidate the optimal role of adjuvant radiation therapy in patients treated with neoadjuvant systemic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The indications for neoadjuvant chemotherapy (NAT) have expanded in recent years both for locally advanced and early-stage breast cancer, with different pathological complete response (pCR) rates among different molecular subtypes. This retrospective two-center study aims to evaluate the diagnostic performance of Contrast-Enhanced Mammography (CEM) in assessing the response to NAT in breast cancer patients. The CEM sensitivity and specificity were 66.2% and 75.2%, with the highest specificity (80.9%) in HR+/HER2− and the highest sensitivity (70%) in triple-negative breast cancer. CEM is a valid tool to assess the pCR with different performances among the molecular subtypes and may be reliable in the decisional process of de-escalating surgical management. Neoadjuvant chemotherapy (NAT) plays a crucial role in breast cancer (BC) treatment, both in advanced BC and in early-stage BC, with different rates of pathological complete response (pCR) among the different BC molecular subtypes. Imaging monitoring is mandatory to evaluate the NAT efficacy. This study evaluates the diagnostic performance of Contrast-Enhanced Mammography (CEM) in BC patients undergoing NAT. This retrospective two-center study included 174 patients. The breast lesions were classified based on the molecular subtypes in hormone receptor (HR+)/HER2−, HER2+, and triple-negative breast cancer (TNBC). The histopathological analysis performed following surgery was used as a reference standard for the pCR. Sensitivity, specificity, PPV, and NPV were measured overall and for the different subtypes. We enrolled 174 patients, 79/174 (46%) HR+/HER2−, 59/174 (33.9%) HER2+, and 35/174 (20.1%) TNBC; the pCR was found in 64/174 (36.8%), of which 57.1% were TNBCs. In the total population, the CEM sensitivity and specificity were 66.2% and 75.2%, with a PPV of 61.4% and an NPV of 78.8%. The highest specificity (80.9%) and NPV (91.7%) were found in HR+/HER2−, while the highest sensitivity (70%) and PPV appeared (73.7%) in TNBC. The results indicate that CEM is a valid tool to assess the pCR, with different performances among the subtypes of BC. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor marking before neoadjuvant systemic therapy (NAST) is an essential part of early breast cancer treatment, aiming to enable adequate surgical excision of the tumor bed in cases with complete clinical regression. Standard surgical techniques for targeted excision generally rely on the invasive insertion of various markers (radiopaque clips, radioactive seeds, silver wire, etc.) into or around the tumor. These techniques are burdened by technical complexity, the risk of complications (hematoma, infection, marker migration, etc.), and limited precision in the insertion and later identification of markers. Herein, we present our original technique of non-invasive three-dimensional tumor localization before and repeatedly during NAST and the preliminary results of its application. Multiple repetitions (monitoring the occasionally eccentric pattern of tumor regression) without the risk of complications suggest a possible advantage over invasive marking techniques. Application in surgical centers lacking trained staff and equipment for invasive tumor marking may impact the quality improvement of post-NAST breast cancer surgery in those centers. Background: We present a detailed description and the preliminary results of our original technique for non-invasive three-dimensional tumor localization in the breast, which was created as an alternative to standard invasive tumor marking before neoadjuvant systemic therapy (NAST), aiming to enable adequate surgery after complete tumor regression. Methods: A detailed description of the technique is provided in the main text. The technique's feasibility and precision were assessed in a single-arm, prospective study based on the histological parameters of the adequacy and rationality of the excision of completely regressed tumor beds. Results: Out of 94 recruited patients, 15 (16%) were deemed unsuitable, mainly due to the tumors' inadequate ultrasound visibility. Among the 79 processed patients, 31 (39%) had complete clinical regression after NAST and were operated on using our technique. The histological parameters of surgical precision (signs of tumor regression: 24/31; microscopic cancer residues: 7/31) were verified in all excised specimens (100% precision). There were no positive margins in seven cases with microscopic residues, indicating our technique's capacity to enable oncologically safe post-NAST surgery. Conclusions: The proposed technique is feasible and satisfactorily accurate in determining the location of regressed tumors, thus representing an alternative to invasive tumor marking, especially in surgical centers lacking trained staff and equipment for invasive marking. The technique's limitations are mainly related to the inadequate ultrasound visibility of the tumor. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is among the most common cancers in women and the fourth leading cause of cancer-related death in females. In developing countries, 6% of diagnoses occur in the advanced stages of the disease. Locally advanced cervical cancer (LACC) is defined as stage IB2-IVA, according to the FIGO 2009 classification. Chemoradiotherapy (CCRT) is the preferred treatment, but 30% of patients relapse after treatment and may suffer from late toxicity. Neoadjuvant chemotherapy (NACT) followed by radical surgery is a common but controversial option, as it can delay curative treatments. Adjuvant surgery after CCRT has shown promising results, with studies indicating potential benefits in disease control and survival rates. However, guidelines mainly suggest exclusive chemoradiotherapy, though a proportion of patients might need additional treatment with surgery. This study compares the oncological outcomes of LACC patients undergoing standard treatments versus those with adjuvant surgery post-CCRT or NACT. Initial findings suggest that adjuvant surgery could improve local control and overall survival in specific patient groups, though further research is needed to confirm these results. Background: The treatment of choice for patients with locally advanced cervical cancer (LACC) is definitive concurrent radio chemotherapy which consists of external beam radiotherapy (EBRT) and concurrent platinum-based chemotherapy (CCRT), with the possible addition of brachytherapy (BT). However, the benefits of adjuvant surgery after neoadjuvant treatments remain a debated issue and a still open question in the literature. This meta-analysis aims to provide an updated view on the controversial topic, focusing on comparing surgery after any adjuvant treatment and standard treatment. Methods: Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, the PubMed and Embase databases were systematically searched in April 2023 for early publications. No limitations on the country were applied. Only English articles were considered. The comparative studies containing data about disease-free survival (DFS) and/or overall survival (OS) were included in the meta-analysis. Results: The CCRT + surgery group showed a significantly better DFS than CCRT (RR 0.69 [95% CI 0.58–0.81] p < 0.01) and a better OS (RR 0.70 [95% CI 0.55–0.89] p < 0.01). Nine studies comparing neoadjuvant chemotherapy (NACT) plus surgery and CCRT were also enrolled. The NACT + surgery group showed a significantly better DFS than CCRT (RR 0.66 [95% CI 0.45–0.97] p < 0.01) and a better OS (RR 0.56 [95% CI 0.38–0.83] p < 0.01). In the sub-analysis of three randomized control trials, the surgery group documented a non-significantly better DFS and OS than CCRT (OR 1.10 [95% CI 0.67–1.80] p = 0.72; I2 = 69% p = 0.72; OR 1.09 [95% CI 0.63–1.91] p = 0.75; I2 = 13% p = 0.32). Conclusion: The results provide updated findings about the efficacy of neoadjuvant treatments, indicating significantly improved DFS and OS in patients undergoing hysterectomy after CCRT or NACT compared with patients undergoing standard treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: A 90-day mortality predictive model for curative gastric cancer resection based on the Spanish EURECCA Esophagogastric Cancer database was externally validated using the GASTRODATA registry. The externally validated model showed a modestly worse performance compared to the original model, nevertheless maintaining its discriminating ability in clinical practice. Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. Methods: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. Results: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. Conclusion: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: The prediction of tumor response after neoadjuvant FLOT therapy is highly necessary. The use of deep learning on gastroesophageal biopsies enabled us to extract predictive information. This prediction model could be easily applied in clinical decision making. Patients could avoid unnecessary treatment or receive an intensified FLOT therapy. Background: The aim of this study was to establish a deep learning prediction model for neoadjuvant FLOT chemotherapy response. The neural network utilized clinical data and visual information from whole-slide images (WSIs) of therapy-naïve gastroesophageal cancer biopsies. Methods: This study included 78 patients from the University Hospital of Cologne and 59 patients from the University Hospital of Heidelberg used as external validation. Results: After surgical resection, 33 patients from Cologne (42.3%) were ypN0 and 45 patients (57.7%) were ypN+, while 23 patients from Heidelberg (39.0%) were ypN0 and 36 patients (61.0%) were ypN+ (p = 0.695). The neural network had an accuracy of 92.1% to predict lymph node metastasis and the area under the curve (AUC) was 0.726. A total of 43 patients from Cologne (55.1%) had less than 50% residual vital tumor (RVT) compared to 34 patients from Heidelberg (57.6%, p = 0.955). The model was able to predict tumor regression with an error of ±14.1% and an AUC of 0.648. Conclusions: This study demonstrates that visual features extracted by deep learning from therapy-naïve biopsies of gastroesophageal adenocarcinomas correlate with positive lymph nodes and tumor regression. The results will be confirmed in prospective studies to achieve early allocation of patients to the most promising treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: High-risk prostate cancer is an aggressive disease, and its treatment can be complex and require the involvement of several specialists. Advances in imaging and therapies in this field can improve survival and help physicians choose the best personalized approach that maintains quality of life. This article summarizes the most recent publications on this condition and its treatments, aiming to provide an updated guide for managing patients with prostate cancer who experience a higher risk of progression and death. The management of high-risk prostate cancer (PCa) presents a significant clinical challenge, often necessitating treatment intensification due to the potential presence of micrometastases. While radical prostatectomy (RP) constitutes one of the primary treatment modalities, the integration of neoadjuvant and adjuvant therapies suggests a paradigm shift towards more aggressive treatment strategies, also guided by new imaging modalities like positron emission tomography using prostate-specific membrane antigen (PSMA-PET). Despite the benefits, treatment intensification raises concerns regarding increased side effects. This review synthesizes the latest evidence on perioperative treatment intensification and de-escalation for high-risk localized and locally advanced PCa patients eligible for surgery. Through a non-systematic literature review conducted via PubMed, Scopus, Web of Science, and ClinicalTrials.gov, we explored various dimensions of perioperative treatments, including neoadjuvant systemic therapies, adjuvant therapies, and the role of novel diagnostic technologies. Emerging evidence provides more support for neoadjuvant systemic therapies. Preliminary results from studies suggest the potential for treatments traditionally reserved for metastatic PCa to show apparent benefit in a non-metastatic setting. The role of adjuvant treatments remains debated, particularly the use of androgen deprivation therapy (ADT) and adjuvant radiotherapy in patients at higher risk of biochemical recurrence. The potential role of radio-guided PSMA lymph node dissection emerges as a cutting-edge approach, offering a targeted method for eradicating disease with greater precision. Innovations such as artificial intelligence and machine learning are potential game-changers, offering new avenues for personalized treatment and improved prognostication. The intensification of surgical treatment in high-risk PCa patients is a dynamic and evolving field, underscored by the integration of traditional and novel therapeutic approaches. As evidence continues to emerge, these strategies will refine patient selection, enhance treatment efficacy, and mitigate the risk of progression, although with an attentive consideration of the associated side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy in breast cancer facilitates breast and axillary surgery and offers significant prognostic value. We present a retrospective cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHER2 in HER2-positive cases. The 10-year estimated disease free survival was 77.3% (95%CI 73.3–81.4%) and the Breast cancer specific survival 83.7% (95%CI 80.3–87.2%). The statistically independent factors related to patient survival were pathology subtype (lobular cancers HR, 4); molecular surrogate subtype (triple negative HR, 4); type of surgery (mastectomy HR, 2), response to chemotherapy (the risk incremented according to the residual cancer burden in 2.2, 4.4 and 8.0 times in I, II and III, respectively) and vascular invasion (HR, 2.4). BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan–Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1–1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. [ABSTRACT FROM AUTHOR]

Simple Summary: Sacrectomy represents a radical indication for bone sarcomas (e.g., osteosarcoma or chondrosarcoma) and chordomas, as well as selected carcinomas with invasion of the sacrum. Extralesional en bloc excision is surgically demanding and associated with resection-induced neurologic deficits and risks. Due to the low incidence of bone sarcomas, the rare localization in the sacrum and the complexity of the surgical procedure, studies reporting on the oncological outcome and corresponding complications in larger patient numbers are rare. The aim was to describe the oncosurgical management and the complication profile and to analyze our own treatment results after partial/total sacrectomy, with attention paid to a possible benefit by using intraoperative 3D navigation. There was a significant difference in progression-free and metastasis-free survival between sarcoma, chordoma and carcinoma patients. Complications were common, but no independently influencing causative factors could be identified. Although there was a subjective impression of improved intraoperative 3D orientation and easier identification of resection planes, the use of navigation did not significantly influence resection status or oncological patient outcome. Introduction: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. Methods: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. Results: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. Conclusions: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Sézary syndrome (SS) is a rare and aggressive form of cutaneous T-cell lymphoma. Despite various treatments, it remains incurable, with a median survival of only 2.1 years. This retrospective study of 17 SS patients in West Sweden from 2012 to 2024 aimed to understand demographic characteristics, treatment effectiveness, and disease progression. Only 35% of patients showed the classic symptoms at diagnosis, indicating the need for personalized diagnostic approaches. Different treatment modalities were used, but combination therapy showed advantages in median survival over monotherapies. Notably, triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP) exhibited the longest median time to the next treatment, at 14.1 months. However, early initiation of ECP did not improve outcomes. This study underscores the complexity of SS, emphasizes the urgent need for more effective treatments, and highlights the importance of future prospective research in optimizing treatment strategies. Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholangiocarcinoma is a rare cancer with a dismal prognosis. The rate of recurrence after treatment of localized disease is high. In this review, we discuss the evidence regarding the use of radiation to improve outcomes in unresectable cholangiocarcinoma. We also discuss studies that have incorporated radiation before and after surgery. The review also briefly highlights recent developments in systemic therapy, especially targeted treatments and immunotherapy. Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome, among patients with gastric cancer. Textbook Neoadjuvant Outcome integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of gastric cancer patients undergoing neoadjuvant chemotherapy to identify the treatment- and patient-related data required to establish high-quality oncological care further. The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of surgery in the combined treatment with hyperthermic intrathoracic chemotherapy of thymoma recurrences and pleural mesothelioma has assumed a controversial role in the context of the multimodal treatment of these diseases, especially when minimally invasive techniques are considered. The authors aim to propose future directions in the approach to these pathologies by placing robotic surgery at the center of reflection, starting, however, from a review of the literature available to date. (1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien–Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a common and challenging disease among men, prompting researchers to explore new ways to understand and manage it effectively. In this review, we focus on a specific type of prostate cancer called intraductal carcinoma (IDC-P), which has unique characteristics and implications for patient care. We aim to clarify the clinical significance of IDC-P and its impact on treatment decisions. Pathological features and molecular aspects offer insights into better risk stratification and treatment approaches for patients with IDC-P. Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P. While the diagnosis of IDC-P relies on specific morphological criteria, its detection remains challenging due to inter-observer variability. Emerging evidence underscores the association of IDC-P with aggressive disease and poor clinical outcomes across various PCa stages. However, standardized management guidelines for IDC-P are lacking. Recent studies suggest considering adjuvant and neoadjuvant therapies in specific patient cohorts to improve outcomes and tailor treatment strategies based on the IDC-P status. However, the current level of evidence regarding this is low. Moving forward, a deeper understanding of the pathogenesis of IDC-P and its interaction with conventional PCa subtypes is crucial for refining risk stratification and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary leiomyosarcoma of bone constitutes less than 0.7% of all primary malignant bone tumors. Currently, there is no consensus on whether therapeutic approaches should align with the biological characteristics seen in soft tissue leiomyosarcoma or be tailored to the bone location. The efficacy of perioperative chemotherapy for this rare tumor type remains uncertain. Our study aimed to assess various treatment modalities across multiple centers. Surgical intervention emerged as the most significant prognostic factor for patient survival in our analysis, with tumors situated axially, indicating poorer prognosis. A considerable portion of patients experienced secondary metastases. Additionally, the perioperative chemotherapy regimens administered did not correlate with enhanced survival outcomes. Hence, the efficacy of perioperative chemotherapy in bone leiomyosarcoma warrants further investigation, alongside the identification of appropriate agents for treatment. Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer presents a challenge due to its high mortality rates and limited treatment options. In an effort to improve patient outcomes, neoadjuvant treatment (NAT) has emerged as a promising approach for both resectable and borderline resectable pancreatic cancer. This scoping review provides a comprehensive overview of evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials, shedding light on the current status of NAT. The efficacy of NAT in terms of survival benefits for patients with resectable pancreatic cancer has been still controversial. However, the efficacy of NAT has been affirmed in cases of borderline resectable pancreatic cancer, although the ideal treatment regimens remain subject to debate. Ongoing trials are actively exploring novel approaches, including immunotherapy, underscoring the dynamic nature of pancreatic cancer treatment. Future efforts aim to refine treatment strategies by integrating systemic chemotherapy with immunotherapy, guided by molecular-based biomarkers to achieve precision oncology. Pancreatic cancer (PC) is a lethal disease that requires innovative therapeutic approaches to enhance the survival outcomes. Neoadjuvant treatment (NAT) has gained attention for resectable and borderline resectable PC, offering improved resection rates and enabling early intervention and patient selection. Several retrospective studies have validated its efficacy. However, previous studies have lacked intention-to-treat analyses and appropriate resectability classifications. Randomized comparative trials may help to enhance the clinical applicability of evidence. Therefore, after searching the MEDLINE database, this scoping review presents a comprehensive summary of the evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials. Diverse regimens and their outcomes were explored for both resectable and borderline resectable PC. While some trials have supported the efficacy of NAT, others have demonstrated no clear survival benefits for patients with resectable PC. The utility of NAT has been confirmed in patients with borderline resectable PC, but the optimal regimens remain debatable. Ongoing trials are investigating novel regimens, including immunotherapy, thereby highlighting the dynamic landscape of PC treatment. Studies should focus on biomarker identification, which may enable precision in oncology. Future endeavors aim to refine treatment strategies, guided by precision oncology. [ABSTRACT FROM AUTHOR]

Simple Summary: This review summarizes the pivotal role of tumor-infiltrating immune cells (TIICs) within the tumor microenvironment (TME) and their impact on cancer prognosis and treatment response. By analyzing TIICs alongside tumor mutation burden (TMB) and immune checkpoint inhibitor (ICI) scores, this study reveals insights into cancer's immune landscapes. Understanding TIICs' influence enables tailored cancer treatments, aiding postoperative care, therapy decisions, and personalized medicine choices. We effectively examined the predictive and prognostic value of TIICs alongside TMB and ICI scores in identifying the diverse immunological environments of cancer. Several approaches discussed in this review provide more accurate predictions of patient outcomes and treatment responses. These models can help identify individuals who may derive greater benefit from adjuvant or neoadjuvant treatment. In summary, we believe that the major contribution of TIICs in cancer will have a substantial positive impact on postoperative follow-up, therapy, interventions, and the ability to make educated decisions regarding personalized cancer treatments. This comprehensive study underscores the significant role of TIICs in combating tumor-mediated immunosuppression and fostering antitumor immune responses, promising improved cancer prognosis and therapeutic outcomes. TIICs are critical components of the TME and are used to estimate prognostic and treatment responses in many malignancies. TIICs in the tumor microenvironment are assessed and quantified by categorizing immune cells into three subtypes: CD66b+ tumor-associated neutrophils (TANs), FoxP3+ regulatory T cells (Tregs), and CD163+ tumor-associated macrophages (TAMs). In addition, many cancers have tumor-infiltrating M1 and M2 macrophages, neutrophils (Neu), CD4+ T cells (T-helper), CD8+ T cells (T-cytotoxic), eosinophils, and mast cells. A variety of clinical treatments have linked tumor immune cell infiltration (ICI) to immunotherapy receptivity and prognosis. To improve the therapeutic effectiveness of immune-modulating drugs in a wider cancer patient population, immune cells and their interactions in the TME must be better understood. This study examines the clinicopathological effects of TIICs in overcoming tumor-mediated immunosuppression to boost antitumor immune responses and improve cancer prognosis. We successfully analyzed the predictive and prognostic usefulness of TIICs alongside TMB and ICI scores to identify cancer's varied immune landscapes. Traditionally, immune cell infiltration was quantified using flow cytometry, immunohistochemistry, gene set enrichment analysis (GSEA), CIBERSORT, ESTIMATE, and other platforms that use integrated immune gene sets from previously published studies. We have also thoroughly examined traditional limitations and newly created unsupervised clustering and deconvolution techniques (SpatialVizScore and ProTICS). These methods predict patient outcomes and treatment responses better. These models may also identify individuals who may benefit more from adjuvant or neoadjuvant treatment. Overall, we think that the significant contribution of TIICs in cancer will greatly benefit postoperative follow-up, therapy, interventions, and informed choices on customized cancer medicines. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study examined how muscle function is affected in cancer patients, particularly those at risk of developing muscle wasting (cachexia). We tested a combination of mild exercise and a protein-rich diet as a potential preventive measure. By analysing muscle fibres from patients undergoing different treatments, we found that cancer cachexia leads to muscle weakness and stiffness. However, our results show that the combined therapy helps maintain muscle flexibility and function. This suggests that such an intervention could improve the quality of life for cancer patients by preserving muscle health. Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC). Little is known about the effects of CC on the biomechanical function of muscle. A promising prevention strategy was found in the form of a multi-modal therapy combining mild resistance exercise (e.g., whole-body electro-myostimulation, WB-EMS) and a protein-rich diet. In a previous study of ours, this was effective in counteracting the loss of muscle mass, yet a systematic and comprehensive assessment of active and passive single muscle fibre functions was so far absent. This pilot study investigated the biomechanical function of single muscle fibres (rectus abdominis) from the biopsies of conventionally treated (pre-)cachectic cancer ((pre-)CC) patients (m = 9), those receiving the multi-modal therapy comprising WB-EMS training and protein-rich nutrition (m = 3), and a control group (m = 5). Our findings not only align with previous findings showing the absolute force loss in CC that is accelerated by atrophy but also speak in favour of a different, potentially energy- and Ca2+-homeostasis-related effect that compromises muscle contraction (F ~0.9 mN vs. F ~0.6 mN in control patients). However, myofibrillar Ca2+ sensitivity and the quality of contraction were unaltered (pCa50: 5.6–5.8). Single fibres from the (pre-)CC patients receiving WB-EMS training and protein supplementation were significantly more compliant (p < 0.001 at ≥130% of resting length L0). Those fibres displayed a similar softness to the ones from the control patients (axial compliance ~15 m/N at ≥130% L0), while single fibres from the patients with (developing) cachexia were significantly stiffer (axial compliance ~7 m/N, p < 0.001 at ≥130% L0). Adjuvant multi-modal therapy (WB-EMS training and nutritional support) contributes to maintaining the axial compliance of single fibres and potentially improves the quality of life for patients at risk of developing CC. [ABSTRACT FROM AUTHOR]

Simple Summary: Radium-223 is used for the management of metastatic castration-resistant prostate cancer. However, the response to this treatment is poor. Targeting the DNA damage response pathway through pharmacological inhibition has the ability to enhance the radiation response. In this study, we investigated the radiosensitising effects of three different DNA damage response inhibitors targeting ATM, ATR, and PARP in combination with X-rays and radium-223 on human prostate cancer cell lines. Their effects on cell survival, DNA double-strand break repair, cell cycle distribution, and apoptosis were evaluated. We determined that these inhibitors increase the ability of X-rays and radium-223 to kill prostate cells to varying degrees. Moreover, inhibition of the DNA damage response pathways impeded the repair of radiation-induced DNA double-strand breaks and induced changes in cell cycle distribution. Altogether, our study determined DDR inhibition as a promising strategy to increase the effectiveness of treatments utilising X-rays and/or 223Ra for localised and metastatic castration-resistant prostate cancer. Radium-223 (223Ra) and Lutetium-177-labelled-PSMA-617 (177Lu-PSMA) are currently the only radiopharmaceutical treatments to prolong survival for patients with metastatic-castration-resistant prostate cancer (mCRPC); however, mCRPC remains an aggressive disease. Recent clinical evidence suggests patients with mutations in DNA repair genes associated with homologous recombination have a greater clinical benefit from 223Ra. In this study, we aimed to determine the utility of combining DNA damage response (DDR) inhibitors to increase the therapeutic efficacy of X-rays, or 223Ra. Radiobiological responses were characterised by in vitro assessment of clonogenic survival, repair of double strand breaks, cell cycle distribution, and apoptosis via PARP-1 cleavage. Here, we show that DDR inhibitors increase the therapeutic efficacy of both radiation qualities examined, which is associated with greater levels of residual DNA damage. Co-treatment of ATM or PARP inhibition with 223Ra increased cell cycle arrest in the G2/M phase. In comparison, combined ATR inhibition and radiation qualities caused G2/M checkpoint abrogation. Additionally, greater levels of apoptosis were observed after the combination of DDR inhibitors with 223Ra. This study identified the ATR inhibitor as the most synergistic inhibitor for both radiation qualities, supporting further pre-clinical evaluation of DDR inhibitors in combination with 223Ra for the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer among women. Metaplastic breast carcinoma is a rare, heterogeneous group of invasive breast carcinomas that are more aggressive, poorly responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than most other breast tumors. This article aims to provide an overview and summary of the current knowledge regarding the translational aspects of metaplastic breast carcinoma that could open the possibility of discovering specific treatment targets and knowing prognostic factors. Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are considered low-grade and the others are high-grade. MpBCs seem to be more aggressive, less responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than other TNBCs. MpBCs have a lower survival rate than expected for TNBCs. MpBC treatment represents a challenge, leading to a thorough exploration of the tumor immune microenvironment, which has recently opened the possibility of new therapeutic strategies. The epithelial–mesenchymal transition in MpBC is characterized by the loss of intercellular adhesion, downregulation of epithelial markers, underexpression of genes with biological epithelial functions, upregulation of mesenchymal markers, overexpression of genes with biological mesenchymal functions, acquisition of fibroblast-like (spindle) morphology, cytoskeleton reorganization, increased motility, invasiveness, and metastatic capabilities. This article reviews and summarizes the current knowledge and translational aspects of MpBC. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we evaluated the status and dynamics of peripheral T cell subpopulations in hepatocellular carcinoma (HCC) patients receiving immune checkpoint blockade with atezolizumab plus bevacizumab (Atez/Bev) treatment and explored biomarkers that are predictive of therapeutic response. The results showed that a higher proportion of CD8+ central memory T cells at baseline is associated with tumor inflammation in HCC, as well as with longer progression-free survival in response to Atez/Bev treatment, especially in cases with an increased proportion of CD8+ effector memory T cells after 3 weeks. Our findings suggest that the peripheral T cell subpopulation can serve as a potential noninvasive biomarker predicting benefits from Atez/Bev treatment. The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear. This study aimed to evaluate the status and dynamics of peripheral T cell subpopulations in HCC patients receiving Atez/Bev treatment and to explore biomarkers predictive of a therapeutic response. We enrolled 83 unresectable advanced HCC patients who commenced Atez/Bev treatment at our hospital between October 2020 and June 2022. Peripheral T cell subpopulations in peripheral blood mononuclear cells at baseline and 3 weeks post-treatment were investigated using flow cytometry and compared with those in control samples from 18 healthy individuals. We retrospectively analyzed the association between peripheral T cell subpopulation profiles and clinical outcomes. Baseline peripheral T cell subpopulations could be profiled in 70 patients with sufficient cell counts, among whom 3-week subpopulations could be evaluated in 51 patients. Multivariate analysis showed that a high baseline proportion of CD8+ central memory T (TCM) cells was independently associated with longer progression-free survival (PFS). Further, overall survival (OS) was significantly prolonged in patients with increased CD8+ effector memory T (TEM) cell proportions. In conclusion, TCM proportion at baseline might be a good indicator of the efficacy of Atez/Bev therapy. Furthermore, observation of increasing TEM proportions might be an early predictor of the potential clinical benefits of treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Aside from a decreased quality of life, patients with esophagogastric tumors often suffer from difficulties with eating that impact nutritional status. Both the presence of cancer and the impacted nutritional status can also reduce muscle mass. All of this can impact treatment decisions: a patient with low muscle mass and low caloric impact might have a lower tolerance for chemotherapy or other treatment courses. However, treating physicians do not always have immediate access to current data on muscle mass and nutritional status. If there was a correlation between quality of life and these parameters, this might allow for the estimation of real-time muscle mass and suggest further controlled studies. (1) Background: Health-related quality of life (HRQoL) gains importance as novel treatment options for individuals with esophagogastric tumors to improve long-term survival. Impaired HRQoL has been shown to be a predictor of overall survival. Sarcopenia is a known prognostic factor for postoperative complications. As the regular control of sarcopenia through CT scans might not always be possible and HRQoL and nutritional scores are easier to obtain, this study aimed to assess the relationship between nutritional scores, HRQoL and skeletal muscle mass in patients undergoing chemotherapy for cancers of the upper gastrointestinal tract. (2) Methods: Eighty patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaire, EORTC's QLQ-C30. Nutritional status was assessed using the MNA, MUST and NRS 2002 scores. Sarcopenia was determined semi-automatically based on the skeletal muscle index at the L3 vertebrae level in staging CT scans. (3) Results: In chemo-naïve patients, HRQoL summary scores correlated significantly with nutritional scores and SMI. SMI and HRQoL prior to neoadjuvant therapy correlated significantly with SMI after treatment. (4) Conclusions: HRQoL is a helpful tool for assessing patients' overall constitution. The correlation of HRQoL summary scores and SMI might allow for a rough assessment of skeletal muscle status through HRQoL assessment in chemo-naïve patients. [ABSTRACT FROM AUTHOR]

Simple Summary: There is little evidence about the optimal timing of systemic chemotherapy (SC) in patients treated with cytoreductive surgery (CRS) and HIPEC for colorectal peritoneal metastases (CRC-PM). Due to the lack of evidence in this field, a systematic literature search and a meta-analysis of relevant studies were performed. Twenty-one studies were included in the systematic review and fifteen in the quantitative analysis (4523 patients). Postoperative SC was associated with increased overall survival compared to no SC or a preoperative SC regimen, whereas SC (pre or post) and pre-SC compared to surgery alone were not. Similar results were found for disease-free survival. Preoperative SC was not associated with an increased risk of severe surgical complications. Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent observations have led to an expansion of the role of neoadjuvant treatment (NAT) as a component of a multidisciplinary approach to the treatment of pancreatic ductal adenocarcinoma (PDAC). However, some issues related to this treatment remain unclear, including (1) the appropriate indications for NAT (as opposed to up-front surgery); (2) predictors of response to NAT; (3) the effect of the response to NAT on the efficacy of postoperative adjuvant chemotherapy (AC); and (4) the establishment of an adjuvant treatment policy based on post-neoadjuvant therapy/surgery histopathological findings. In this article, we discuss these issues based on a review of the literature and the authors' own experience of NAT using gemcitabine plus S-1. In addition to established evidence of the efficacy of adjuvant chemotherapy (AC) for pancreatic ductal adenocarcinoma (PDAC), evidence of the effects of neoadjuvant treatments (NATs), including chemotherapy and chemoradiotherapy, has also been accumulating. Recent results from prospective studies and meta-analyses suggest that NATs may be beneficial not only for borderline resectable PDAC, but also for resectable PDAC, by increasing the likelihood of successful R0 resection, decreasing the likelihood of the development of lymph node metastasis, and improving recurrence-free and overall survival. In addition, response to NAT may be informative for predicting the clinical course after preoperative NAT followed by surgery; in this way, the postoperative treatment strategy can be revised based on the effect of NAT and the post-neoadjuvant therapy/surgery histopathological findings. On the other hand, the response to NAT and AC is also influenced by the tumor biology and the patient's immune/nutritional status; therefore, planning of the treatment strategy and meticulous management of NAT, surgery, and AC is required on a patient-by-patient basis. Our experience of using gemcitabine plus S-1 showed that this NAT regimen achieved tumor shrinkage and decreased the levels of tumor markers but failed to provide a survival benefit. Our results also suggested that response/adverse events to NAT may be predictive of the efficacy of AC, as well as survival outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality. In the last decade, a breakthrough in the treatment landscape of HCC has been experienced. The unprecedented number of therapeutic options for advanced stages has made the selection of sequence strategies more complex and the need for biomarkers of treatment response or tumor escape more urgent. The understanding of molecular events leading to drug resistance has identified noncoding RNAs as promising therapeutic targets. Preclinical studies testing the combined efficacy of noncoding RNAs and clinically available drugs represent a crucial step to prevent/limit the onset of drug resistance in advanced cases. The incidence of hepatocellular carcinoma (HCC) is increasing, and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinically available treatments has dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients, showing a durable treatment benefit over time and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although there is improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with nonviral etiologies, such as nonalcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers that are informative of the best treatment approach are required actions to improve patient survival. Abundant evidence indicates that noncoding RNAs (ncRNAs) are pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular-targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy plays a crucial role in managing lymphomas. Advancements in radiation oncology have resulted in smaller treatment volumes and an improved ability to avoid nearby critical tissues and organs. Additionally, radiation therapy doses have been reduced. Our retrospective study aimed to compare the efficacy and side effects of involved-field (IFRT) versus involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma. Addressing the persistent concern of radiotherapy toxicity, our findings highlight that scaling down the treatment volume and doses maintains efficacy and local control without compromising patient outcome. Furthermore, this approach significantly reduces both acute and long-term side effects. (1) Background: This study aimed to examine the difference in efficacy and toxicity of involved-field (IFRT) and involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma patients. (2) Methods: In total, 140 patients with infradiaphragmal lymphoma treated between 2003 and 2020 were retrospectively evaluated. There were 69 patients (49%) treated with IFRT, and 71 (51%) patients treated with ISRT. The median dose in the IFRT group was 36 Gy, (range 4–50.4 Gy), and in the ISRT group, it was 30 Gy (range 4–48 Gy). (3) Results: The median follow-up in the IFRT group was 133 months (95% CI 109–158), and in the ISRT group, it was 48 months (95% CI 39–57). In the IFRT group, locoregional control was 67%, and in the ISRT group, 73%. The 2- and 5-year overall survival (OS) in the IFRT and ISRT groups were 79% and 69% vs. 80% and 70%, respectively (p = 0.711). The 2- and 5-year event-free survival (EFS) in the IFRT and ISRT groups were 73% and 68% vs. 77% and 70%, respectively (p = 0.575). Acute side effects occurred in 43 (31%) patients, which is more frequent in the IFRT group, 34 (39%) patients, than in the ISRT group, 9 (13%) patients, p > 0.01. Late toxicities occurred more often in the IFRT group of patients, (10/53) 19%, than in the ISRT group of patients, (2/37) 5%, (p = 0.026). (4) Conclusions: By reducing the radiotherapy volume and the doses in the treatment of infradiaphragmatic fields, treatment with significantly fewer acute and long-term side effects is possible. At the same time, efficiency and local disease control are not compromised. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is sometimes diagnosed at an advanced stage, with subsequent complex therapeutic efforts combining both locoregional and systemic treatments. Computed tomography and magnetic resonance are conventionally used for post-treatment follow-up of HCC. Contrast-enhanced ultrasound and dynamic contrast-enhanced ultrasound (DCE-US) have gained an increasing importance due to the interest of several researchers in their potential role in the early assessment of response to locoregional treatments or antiangiogenic therapies in patients with advanced HCC. Particularly, DCE-US allows the construction of time–intensity curves, providing an assessment of the parameters related to neoplastic tissue perfusion and its potential changes following therapies. Its advantage resides in being easily repeatable, minimally invasive, and able to grant important evaluations about patients' survival, essential for well-timed therapeutic changes in case of unsatisfying response and eventual further treatment planning. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the sixth most common malignant tumor in the world, with an incidence of 2–8% per year in patients with hepatic cirrhosis or chronic hepatitis. Despite surveillance schedules, it is sometimes diagnosed at an advanced stage, requiring complex therapeutic efforts with both locoregional and systemic treatments. Traditional radiological tools (computed tomography and magnetic resonance) are used for the post-treatment follow-up of HCC. The first follow-up imaging is performed at 4 weeks after resection or locoregional treatments, or after 3 months from the beginning of systemic therapies, and subsequently every 3 months for the first 2 years. For this reason, these radiological methods do not grant the possibility of an early distinction between good and poor therapeutic response. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced ultrasound (DCE-US) have gained the interest of several researchers for their potential role in the early assessment of response to locoregional treatments (chemoembolization) or antiangiogenic therapies in patients with advanced HCC. In fact, DCE-US, through a quantitative analysis performed by specific software, allows the construction of time–intensity curves, providing an evaluation of the parameters related to neoplastic tissue perfusion and its potential changes following therapies. It has the invaluable advantage of being easily repeatable, minimally invasive, and able to grant important evaluations regarding patients' survival, essential for well-timed therapeutic changes in case of unsatisfying response, and eventual further treatment planning. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral endocrine therapy is a key component of breast cancer treatment in hormone-positive patients, the most frequent subtype of this cancer. Adherence to this treatment is a factor related to an increased probability of relapse and death. The COVID-19 pandemic has had a disruptive impact on the use of cancer services, delaying diagnosis and stopping screening during the peak of the pandemic. We assessed the impact of the COVID-19 on the adherence to oral endocrine therapy in Catalonia (Spain) using the data collected in the clinical records of the public health care system. We have found that the first wave of the COVID-19 (between March and September 2020) was associated with a modest impact on treatment adherence. Purpose. To assess the impact of the COVID-19 pandemic on adherence to oral endocrine therapy in patients diagnosed with breast cancer in the public healthcare system in Catalonia (Spain). Methods. Retrospective cohort study in patients starting endocrine therapy from 2017 to 2021. Adherence was measured during the first year of treatment, and the impact of the pandemic was calculated according to the calendar year and whether the first year of treatment included the peak period of the pandemic in our setting (March–September 2020). Analyses were performed using a chi-square test and multivariable logistic regression, with results stratified by year, age group, and drug type. Results. Mean overall adherence during the first year of treatment was 89.6% from 2017 to 2021. In contrast, the patients who started treatment in 2019 and 2020 and whose treatment included the peak pandemic period presented an adherence of 87.0% and 86.5%, respectively. Young age and tamoxifen or combination therapy were predictors of low adherence. An increase in neoadjuvant therapy was also observed in 2020. Conclusions. The COVID-19 pandemic had only a modest impact on adherence to endocrine therapy (≈3%), despite the enormous disruptions for patients, the healthcare system in general, and cancer care in particular that were occurring in that period. [ABSTRACT FROM AUTHOR]