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Introduction: Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT—whether induction chemotherapy should precede or follow chemoradiotherapy—remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. Methods: Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high‐quality studies, specific inclusion and exclusion criteria were applied. Results: The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO‐12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. Conclusion: This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies. [ABSTRACT FROM AUTHOR]

Esophagogastric adenocarcinoma (EGJ‐AC) poses a significant global health burden, characterized by high incidence rates and poor prognosis. Despite advancements in treatment modalities, including surgery, chemotherapy, and radiation therapy (RT), locally advanced EGJ‐AC management remains challenging. Various preclinical and clinical studies have provided insights into the synergistic effects of combining immune checkpoint inhibitors (ICIs) with RT, further supporting the combination therapy in EGJ‐AC. Immunotherapy, particularly ICIs, has emerged as a promising therapeutic approach in various malignancies, including EGJ‐AC. This narrative review aims to critically examine the rationale behind combining ICIs with standard treatment modalities, including RT or chemoradiotherapy, in the preoperative setting for locally advanced EGJ‐AC. A comprehensive literature search identified eight phase 2 randomized clinical trials evaluating the safety profile and oncologic outcomes of adding ICI agents to neoadjuvant chemoradiotherapy in this population. The results of enrolled trials show that the combination of ICIs with standard treatment modalities is a promising approach for improving survival and pathological response in patients with locally advanced EGJ‐AC. This combination treatment was associated with mostly grade 1–2 immune‐related toxicities, indicating its safety and tolerability. There were higher rates of complete or major pathologic responses compared to historical controls. Further studies, including large‐scale randomized controlled trials, are needed to address remaining questions regarding the efficacy, safety, and long‐term outcomes of combination therapy in this population. [ABSTRACT FROM AUTHOR]

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Purpose: Sinonasal malignancies are a rare group of head and neck cancers. We aimed to report the oncological outcomes based on histological types in patients who underwent radiotherapy. Materials and Methods: In this single-institution study, we retrospectively retrieved and analyzed data of patients with sinonasal carcinomas who underwent radiotherapy during 2011-2016 as part of their treatment. The 3-year rate of local, regional, and distant recurrences, and overall survival were evaluated according to the histological type. Results: A total of 28 patients were evaluated in this study, the majority of whom were male (60%). Squamous cell carcinoma (SCC), adenoid cystic carcinoma (ACC), and adenocarcinoma (ADC) were found in 15 patients (53.5%), 8 (28.5%), and 5 (18%), respectively. The highest rates of local and regional recurrences were observed in ACC and SCC, respectively. Distant recurrences were numerically more common in ADC. The 3-year OS was 48%, 50%, and 73% in SCC, ADC, and ACC, respectively. Conclusion: Different histopathologies of sinonasal cancer seem to have different patterns of failure, and this may be considered in the treatment approach. [ABSTRACT FROM AUTHOR]

The treatment of locally advanced rectal cancer (LARC) is a challenging situation for radiation oncologists and colorectal surgeons. Most current approaches recommend neoadjuvant fluorouracil or capecitabine-based chemoradiotherapy followed by surgery as a standard of care. Intensification of concurrent chemotherapy by adding oxaliplatin to fluorouracil or capecitabine backbone to get better outcomes is the matter that has remained unresolved. In this review, we searched Medline and Google Scholar databases and selected 28 prospective phase II and III clinical trials that addressed this question. We discussed the potential advantages and drawbacks of incorporating oxaliplatin into concurrent chemoradiation therapy. We tried to define whether adding oxaliplatin to concurrent chemoradiation with excellent performance and high-risk features benefits some subpopulations. The available literature suggests that by adding oxaliplatin there are some benefits in enhancing response to neoadjuvant chemoradiotherapy, however, without any translated improvements in long-term outcomes including overall and disease-free survival. [ABSTRACT FROM AUTHOR]

Background and purpose: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. Materials and methods: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. Results: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. Conclusion: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques. [ABSTRACT FROM AUTHOR]

Background: Hypopharyngeal carcinoma (HPC) is a rare head and neck cancer which poses many therapeutic challenges. There is limited evidence regarding the outcomes of HPC treatment in Iran. Method: In this retrospective cohort study, we evaluated patients treated with chemoradiation or radiation alone, between 2007 and 2016 in the radiation oncology ward of the cancer institute affiliated to Tehran University of Medical Sciences. The design of the study was reviewed and approved by the local institutional review board (code: 86100142). All patients underwent definitive radiotherapy with or without concurrent or sequential chemotherapy. We assessed the two-year overall survival (OS) as the primary outcome. The progression-free survival (PFS) was our secondary outcome. Results: We studied 40 patients whose median age was 58 years. 37 patients were stage 3 or 4, while the most common stage was T3N1-2, observed in 35% of the cases. The most common site of involvement was pyriform sinus (47.5%). The twoyear OS rate was 29%. The two-year PFS was 22%. In the univariate analysis, N0-1 vs. N 2-3 and stage 2 vs. stage 3-4 were significant predictors of OS. In addition, distant metastasis had almost a significant association with lower OS. Conclusion: The outcome of locally advanced HPC was not promising using 3DCRT alone. It is necessary to implement dramatic changes in the management of these patients to achieve better outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The COVID‐19 pandemic has caused significant morbidity and mortality thus far. Considering the historical uses of high‐voltage X‐ray beams for unresolvable pneumonia, we aimed to assess whether low‐dose whole‐lung irradiation (WLI) could provide any benefits for patients with refractory COVID‐19 pneumonia. Methods: Eleven patients with refractory COVID‐19 pneumonia were treated with WLI to a total dose of 1 Gy and compared to 11 patients in a matched control group from June to November 2020. The study's primary endpoint was improvement of chest X‐ray severity score (CXRS), followed by changes in mean oxygen (O2) saturation and 28‐day mortality as secondary endpoints. Results: The final CXRS was significantly lower in the WLI group (8.7 ± 2.5) compared to the control group (12.3 ± 3.3) (P: 0.016). Change of CXRS from the first to the last chest X‐ray was −2.2 ± 3.1 for the WLI group and 0.7 ± 3.9 for the control group, which showed a trend for lower CXRS in the WLI group (U = 30, p: 0.085). Mean O2 saturation showed insignificant improvement in the first 24 hours after radiotherapy (mean difference: 2.5 ± 4.1, Z=−1.6, P value: 0.11). Overall survival after 28 days was 32% in the WLI group and 11% in the control group (P: 0.48). The reason for death in many patients was not merely respiratory failure, but also other adverse situations like pneumothorax, cardiogenic shock and pulmonary thromboembolism. Conclusions: Low‐dose WLI could improve the CXR severity score and O2 saturation in severely ill COVID‐19 patients, but larger studies are required to determine its impact on mortality. [ABSTRACT FROM AUTHOR]

Rectal cancer is one of the most prevalent cancers in the world. In many countries, the current standard of care is long-course chemoradiation (CRT), followed by total mesorectal excision. Some efforts have been made by intensifying radiation or chemotherapy components of the neoadjuvant therapy to further decrease the local recurrence and augment surgery's feasibility and improve the oncological outcomes. This paper reviews recent intensified neoadjuvant interventions in locally advanced rectal cancer (LARC) in terms of efficacy and treatment-related toxicity. Many maneuvers have been made so far to improve the oncological outcomes of rectal cancer with intensified neoadjuvant longcourse CRT. Some of these approaches seem compelling and deserve further study, while some have just increased the treatment-related toxicities without evident benefits. Those endeavors with greater pathological complete response than the standard of care may make us await the long-term results on survival rates and chronic treatment-related toxicity. After introduction of neoadjuvant CRT for LARC there have been many efforts to improve its outcomes. Here, this study gathered most of these efforts that intensified the neoadjuvant therapy with some being promising and some being futile. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates. [ABSTRACT FROM AUTHOR]

Background: Colorectal carcinoma is one of most common cancers in Iran with increasing incidence. The mean age of the affected is decreasing. With progresses in multimodality treatment, we witnessed improved prognosis in colorectal cancers. Objectives: This study aimed at evaluating the outcomes of patients with rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy followed by surgery. Methods: In this retrospective cohort study, we assessed the oncologic treatment outcomes of patients with locally advanced (T3-4 or N+ve) rectal adenocarcinoma in our high volume cancer center, Iran cancer institute, Tehran, Iran. Patients with synchronous metastasis, previous malignancy, and history of pelvic radiation were excluded. The primary endpoint was overall survival (OS) rate and secondary endpoints were disease-free survival and pathologic response. Results: Of patients being treated between 2008 and 2014, 158 were entered to final analysis; they completed planned neoadjuvant treatment and retuned after surgery with pathology report. The mean age was 56 years and mean interval from radiotherapy to surgery was 9 weeks. Thirty percent achieved pathologic complete response. Two-year overall and disease-free survival rate was 87% and 80%, respectively. In multivariate analysis age, sex, local recurrence, clinical stage, and radiotherapy to surgery interval failed to predict OS. The pathologic response (complete vs. non-complete) and the absence of distant metastasis were independent predictors of OS. Conclusions: The rate of pathologic response and survival in our series was comparable to other big randomized studies in the world and even better than previous national reports. These findings emphasize the necessity of treating patients with locally advanced rectal cancer in high volume centers. [ABSTRACT FROM AUTHOR]

Tongue squamous cell carcinoma (TSCC) is one of the most prevalent types of head and neck malignancies, and its treatment typically involves surgery combined with radiotherapy and chemotherapy. Despite advancements in treatment, TSCC recurrence remains a significant concern, affecting approximately 20% of treated patients. This study aims to assess the impact of the time interval between radiotherapy and surgery on oncological outcomes in TSCC patients. A total of 215 patient records (98 females and 117 males) with biopsy-proven TSCC receiving various treatments were extracted. The Inclusion criteria were patients who received external beam radiotherapy, had no detectable metastasis, underwent oncological surgery, and received a minimum radiation dose of 60 Gy. Ultimately, 108 patients met these criteria and were included in the analysis. The surgical procedure involved glossectomy, and the prescribed radiotherapy dose exceeded 60 Gy. Patients were stratified based on tumor stage (early-stage and locally advanced stage) and the timing of radiotherapy initiation after surgery (less than 47 days and more than 47 days). The study analyzed loco-regional control, loco-regional recurrence, disease-free survival, and overall survival as endpoints. These endpoints were compared between different subgroups based on tumor stage and surgery to radiotherapy interval. A retrospective analysis was conducted on the medical records of 108 patients who underwent surgical treatment followed by radiotherapy between 2011 and 2022. In early-stage patients, radiotherapy within 47 days after surgery demonstrated superior disease-free survival (DFS) outcomes. However, in locally advanced-stage patients, the opposite trend was observed, with a longer interval between surgery and radiotherapy associated with improved DFS outcomes. These patterns were similarly reflected in overall survival (OS) outcomes. Notably, the difference in loco-regional recurrence (LLR) outcomes was more pronounced among advanced-stage patients. In conclusion, this study highlights that advanced-stage TSCC patients tend to experience earlier recurrence, potentially necessitating additional surgical interventions or precluding the administration of radiotherapy, as investigated in our study. These findings shed light on the significance of the time interval between surgery and radiotherapy in TSCC management. [ABSTRACT FROM AUTHOR]