Search

What is known and objective: Chemotherapy drugs are often administered in combinations with predefined interdependent doses and cycle intervals. As yet, there is no global standardization system to describe these complex regimens in a universally comprehensive manner. The aim of this review is to identify which efforts for standardization have been undertaken and which recommendations for databases and nomenclature of chemotherapy regimens are available. Methods: A literature review was performed to identify all peer‐reviewed full‐text articles about oncology therapy regimen codification. In addition, the results of this search were evaluated and consensus recommendations from a European expert panel were subsequently added. Results: This review gives an overview of attempts to standardize chemotherapy nomenclature described in the literature, as well as of previously published identified gaps in regimen codification. In addition, we summarized the suggestions for improvement of chemotherapy codification found in the available literature, combining them with the expertise from a European expert panel of oncology pharmacists. What is new and conclusions: We believe that one of the most important error‐prevention measures is standardization. However, there is a paucity of data how it may be achieved. Currently available data suggest that standardization has a positive impact on usability for data networks, prescription software, safety and the measurement of the quality of cancer care delivery. Standardization is also a strong pre‐requisite for all discussions including oncology pharmacists and oncologists when evaluating chemotherapy regimen in countries in Europe but also all over the world. The recommendations compiled in this review can help to support overdue standardization efforts in this important therapeutic area. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT., Methods: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×10 3 cells/μL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination., Results: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1)., Conclusions: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-60/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Summary: Additional data on blast phase (BP) chronic myeloid leukaemia (CML) in children and adolescents is essential for improving diagnostic and therapeutic approaches of this rare but serious condition. Here, we describe distinct clinical and genetic characteristics of 18 paediatric patients with de novo (n = 10) and secondary (n = 8) BP CML enrolled in the CML‐PAED‐II trial and registry. Our findings suggest that paediatric patients exhibit a diverse cytogenetic profile compared to adults with BP CML. In addition, patients with de novo BP CML in this cohort presented at a younger age, whereas patients with secondary BP CML more often harboured complex karyotypes. [ABSTRACT FROM AUTHOR]

Purpose: About 30%–35% of nonmetastatic and 60%–80% of metastatic Ewing Sarcoma (ES) will relapse post-treatment and outcomes after relapse continue to be poor over last several decades. Prognostic factors affecting survival after relapse of ES are also not robustly known. We present outcomes using a novel hybrid salvage protocol of four active chemotherapeutic agents in our cohort of patients after relapse of ES. Methods: This is a retrospective analysis of all consecutive relapsed ES patients treated with curative intent over 4 years (January 2012 to December 2015). All received 12-cycles of hybrid chemotherapy regimen with surgery/radiotherapy done after first 4 cycles. Event-free survival (EFS)/overall survival (OS) estimates were analyzed by Kaplan–Meier product-limit estimator. Cox regression analysis was performed to identify prognostic factors predicting outcome in relapsed ES. Results: Salvage regimen was given to 53/108 relapsed ES patients with the rest having opted for palliation upfront. Median age of the treated patients was 19 years (range: 4–40); male:female ratio was 2.7:1. Median time to first relapse was 18.8 months (range: 2.2–91). While 41/53 patients (77%) completed salvage therapy, 6 (11.3%) progressed and 6 (11.3%) abandoned treatment. Median follow-up of the study cohort is 31 months (range: 4–81). Of the analyzable cohort (n = 47), 30 (64%) had a second relapse or progression on salvage treatment. At last follow-up, 31 patients had died (including one due to toxicity and rest due to disease) and 16 patients were alive (14 with no active disease and 2 with disease). The 4-year EFS and OS are 28% and 37%, respectively, for the entire cohort. While adolescents and young adult patients (AYA) had a better survival (p-0.041), relapsed ES patients with shorter disease-free interval (DFI) (<24 months) had a poorer survival (p-0.004). The type of relapse (local or metastatic or combined) after primary treatment did not affect outcome after salvage therapy. Conclusions: We have used a novel hybrid chemotherapy protocol using four active agents in relapsed ES, which is well tolerated and shows promising results. Older age (≥15 years) and longer DFI (>24 months) portend better survival post-relapse. In our cohort of relapsed ES, AYAs fared better than others and type of relapse after primary treatment did not affect outcome after salvage therapy. [ABSTRACT FROM AUTHOR]

Shuisheng Zhang,1,2 Weimin Xie,3 Yinghua Zou,4 Shuanghua Xie,5 Jianwei Zhang,1 Wei Yuan,6,7 Jie Ma,6–8 Jiuda Zhao,9 Cuiling Zheng,10 Yingtai Chen,1 Chengfeng Wang1 1Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 2Department of General Surgery, Peking University Third Hospital, 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 4Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, 5Department of Cancer Epidemiology and Health Statistics, 6State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 7Clinical Immunology Center, Chinese Academy of Medical Science, 8Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Beijing, 9Department of Medical Oncology, Affiliated Hospital of Qinghai University, Xining, 10Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Background: Systemic chemotherapy is the standard treatment for locally advanced and metastatic pancreatic cancer, but there is no consensus on the optimum regimen. We aimed to compare and rank the locally advanced and metastatic pancreatic adenocarcinoma chemotherapy regimens evaluated in randomized controlled trials (RCTs) in the past 15 years.Materials and methods: PubMed, Embase, Cochrane Collaboration database, and ­ClinicalTrials.gov were searched for RCTs comparing chemotherapy regimens as first-line treatment for locally advanced and metastatic pancreatic adenocarcinomas. By using Bayesian network meta-analysis, we compared and ranked all included chemotherapy regimens in terms of overall survival, progression-free survival, response rate, and hematological toxicity.Results: The analysis included 68 RCTs, with 14,908 patients and 63 treatment strategies. For overall survival, NSC-631570 (hazard ratio [HR] vs gemcitabine monotherapy 0.44, 95% credible interval: 0.24–0.76) and gemcitabine+NSC-631570 (HR 0.45, 0.24–0.86) were the two top-ranked chemotherapy regimens. For progression-free survival, PEFG (cisplatin + epirubicin + fluorouracil + gemcitabine) ranked first (HR 0.51, 0.34–0.77). PG (gemcitabine + pemetrexed) (odds ratio [OR] 4.68, 2.24–9.64) and FLEC (fluorouracil + leucovorin + epirubicin + carboplatin) (OR 4.52, 1.14–24.00) were ranked the most hematologically toxic, with gastrazole having the least toxicity (OR 0.03, 0.00–0.46).Conclusion: The chemotherapy regimens NSC-631570 and gemcitabine+NSC-631570 were ranked the most efficacious for locally advanced and metastatic pancreatic adenocarcinomas in terms of overall survival, which warrants further confirmation in large-scale RCTs. Keywords: locally advanced and metastatic pancreatic adenocarcinoma, chemotherapy regimen, overall survival, rank

Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type [WT] RAS mCRC. Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m2 twice daily on days 1–14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 [26%], 1 [67%], 2 [7%]) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7–63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5–10.4) months, and median TTR was 2.2 (1.9–2.8) months. Median TTP was 9.6 (4.8–11.5) months, with a median TTF of 5.2 (2.8–7.2) months. The median PFS was 7.5 (4.4–10.4) months, and the median OS was 23.7 (7.4–27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3–4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related. This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC. • Panitumumab has a low rate of immunogenicity compared with other antibodies against EGFR because of its fully human nature. • The combination of panitumumab and capecitabine was suggested to be effective in older patients with WT RAS mCRC. • The good tolerability and safety profile of the combination were in line to previous studies in older patients. • Panitumumab with capecitabine may provide an alternative to other anti-EGFR regimens in older patients with WT RAS mCRC. [ABSTRACT FROM AUTHOR]

Modulating epigenetic modification has been recognized for over a decade as an effective therapeutic approach to cancer and many studies of histone deacetylase (HDAC), one of the best known epigenetic modulators, have been published. HDAC modulates cell proliferation and angiogenesis and plays an essential role in cell growth. Research shows that up-regulated HDACs are present in many cancer types and synthetic or natural HDAC inhibitors have been used to silence overregulated HDACs. Inhibiting HDACs may cause arrest of cell proliferation, angiogenesis reduction and cell apoptosis. Recent studies indicate that HDAC inhibitors can provide a therapeutic effect in various cancers, such as B-cell lymphoma, leukemia, multiple myeloma and some virus-associated cancers. Some evidence has demonstrated that HDAC inhibitors can increase the expression of immune-related molecules leading to accumulation of CD8 + T cells and causing unresponsive tumor cells to be recognized by the immune system, reducing tumor immunity. This may be a solution for the blockade of PD-1. Here, we review the emerging development of HDAC inhibitors in various cancer treatments and reduction of tumor immunity.

Objectives: Primary cutaneous clear cell sarcoma (PCS) is a rare malignancy and difficult to differentiate from melanoma. We investigated factors influencing survival and recurrence.Methods: An institutional cancer registry and literature search were used for a retrospective study. Only clear cell sarcoma cases with a primary site of skin and subcutaneous tissue were included. Kaplan-Meier and Cox regression analyses were used to assess survival time and hazard ratios.Results: Three eligible cases were identified at our institution. In addition, the PubMed and Google Scholar reviews identified 1,878 items, with 23 patients with PCS. The median age was 25 years with 62% female. The tumors ranged in size from 0.4 to 4.5 cm. Cytogenetics showed t(12;22)(q13;q12) in all cases and a unique variant of t(2;22)(q32.3;q12) in one case. Surgery was the most common treatment, followed by chemotherapy/radiation. PCS recurred in 46% of patients with a median relapse-free survival time of 15 months. Only two known PCS-related mortalities were recorded, at 38 and 60 months following initial diagnosis. Smaller tumor size and negative sentinel lymph node biopsy (SLNB) status were significantly associated with a better disease-free survival.Conclusions: Tumor size and SLNB status influence PCS survival and recurrence. More research is needed due to the rarity of this disease. [ABSTRACT FROM AUTHOR]

Breast cancer is characterized by histological and functional heterogeneity, posing a clinical challenge for patient treatment. Emerging evidence suggests that the distinct subtypes reflect the repertoire of genetic alterations and the target cell. However, the precise initiating events that predispose normal epithelium to neoplasia are poorly understood. Here, we demonstrate that breast epithelial organoids can be generated from human reduction mammoplasties (12 out of 12 donors), thus creating a tool to study the clonal evolution of breast cancer. To recapitulate de novo oncogenesis, we exploited clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 for targeted knockout of four breast cancer-associated tumor suppressor genes (P53, PTEN, RB1, NF1) in mammary progenitor cells from six donors. Mutant organoids gained long-term culturing capacity and formed estrogen-receptor positive luminal tumors on transplantation into mice for one out of six P53/PTEN/RB1-mutated and three out of six P53/PTEN/RB1/NF1-mutated lines. These organoids responded to endocrine therapy or chemotherapy, supporting the potential utility of this model to enhance our understanding of the molecular events that culminate in specific subtypes of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Treatment failures in cancers, including multiple myeloma (MM), are most likely due to the persistence of a minor population of tumor-initiating cells (TICs), which are noncycling or slowly cycling and very drug resistant.Methods: Gene expression profiling and real-time quantitative reverse transcription polymerase chain reaction were employed to define genes differentially expressed between the side-population cells, which contain the TICs, and the main population of MM cells derived from 11 MM patient samples. Self-renewal potential was analyzed by clonogenicity and drug resistance of CD24+ MM cells. Flow cytometry (n = 60) and immunofluorescence (n = 66) were applied on MM patient samples to determine CD24 expression. Therapeutic effects of CD24 antibodies were tested in xenograft MM mouse models containing three to six mice per group.Results: CD24 was highly expressed in the side-population cells, and CD24+ MM cells exhibited high expression of induced pluripotent or embryonic stem cell genes. CD24+ MM cells showed increased clonogenicity, drug resistance, and tumorigenicity. Only 10 CD24+ MM cells were required to develop plasmacytomas in mice (n = three of five mice after 27 days). The frequency of CD24+ MM cells was highly variable in primary MM samples, but the average of CD24+ MM cells was 8.3% after chemotherapy and in complete-remission MM samples with persistent minimal residual disease compared with 1.0% CD24+ MM cells in newly diagnosed MM samples (n = 26). MM patients with a high initial percentage of CD24+ MM cells had inferior progression-free survival (hazard ratio [HR] = 3.81, 95% confidence interval [CI] = 5.66 to 18.34, P < .001) and overall survival (HR = 3.87, 95% CI = 16.61 to 34.39, P = .002). A CD24 antibody inhibited MM cell growth and prevented tumor progression in vivo.Conclusion: Our studies demonstrate that CD24+ MM cells maintain the TIC features of self-renewal and drug resistance and provide a target for myeloma therapy. [ABSTRACT FROM AUTHOR]

Background: Non-Hispanic black (NHB) adults with cancer may have longer time-to-treatment than non-Hispanic whites (NHW) in the United States. Unequal access to medical care may partially account for this racial disparity. This study aimed to investigate whether there were racial differences in time-to-treatment and in treatment delays for patients diagnosed with colon cancer in the equal-access Military Health System (MHS).Methods: Patients age 18-79 years diagnosed with colon adenocarcinoma between January 1, 1998, and December 31, 2014, were identified in the Department of Defense Central Cancer Registry and the MHS Data Repository-linked databases. Median time-to-treatment (surgery and chemotherapy) and 95% confidence intervals were compared between NHBs and NHWs in multivariable quantile regression models. Odds ratios and 95% confidence intervals of receiving delayed treatment defined by guidelines for NHBs relative to NHWs were estimated using multivariable logistic regression.Results: Patients (n = 3067) had a mean age at diagnosis of 58.4 (12.2) years and the racial distribution was 76.7% NHW and 23.3% NHB. Median adjusted time-to-treatment was similar for NHB compared to NHW patients. The likelihood of receiving delayed treatment was similar between NHB and NHW patients.Conclusions: In the MHS, there was no evidence of treatment delays for NHBs compared to NHWs, suggesting the role of equal access to medical care and insurance coverage in reducing racial disparities in colon cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Tumor growth can be addicted to vital oncogenes, but whether long noncoding RNAs (lncRNAs) are essential to cancer survival is largely uncharacterized.Methods: We retrieved Gene Expression Omnibus datasets to identify lncRNA overexpression in 257 cancers vs 196 normal tissues and analyzed the association of ST8SIA6-AS1 (termed Aurora A/Polo-like-kinase 1 [PLK1]-associated lncRNA, APAL) with the clinical outcomes of multiple types of cancer from public RNA sequencing and microarray datasets as well as from in-house cancer cohorts. Loss- and gain-of-function experiments were performed to explore the role of APAL in cancers in vitro and in vivo. RNA pulldown and RNA immunoprecipitation were used to investigate APAL-interacting proteins. All statistical tests were two-sided.Results: APAL is overexpressed in multiple human cancers associated with poor clinical outcome of patients. APAL knockdown causes mitotic catastrophe and massive apoptosis in human breast, lung, and pancreatic cancer cells. Overexpressing APAL accelerates cancer cell cycle progression, promotes proliferation, and inhibits chemotherapy-induced apoptosis. Mechanism studies show that APAL links up PLK1 and Aurora A to enhance Aurora A-mediated PLK1 phosphorylation. Notably, targeting APAL inhibits the growth of breast and lung cancer xenografts in vivo (MCF-7 xenografts: mean tumor weight, control = 0.18 g [SD = 0.03] vs APAL locked nucleic acids = 0.07 g [SD = 0.02], P < .001, n = 8 mice per group; A549 xenografts: mean tumor weight control = 0.36 g [SD = 0.10] vs APAL locked nucleic acids = 0.10 g [SD = 0.04], P < .001, n = 9 mice per group) and the survival of patient-derived breast cancer organoids in three-dimensional cultures.Conclusions: Our data highlight the essential role of lncRNA in cancer cell survival and the potential of APAL as an attractive therapeutic target for a broad-spectrum of cancers. [ABSTRACT FROM AUTHOR]

For nasopharyngeal carcinoma (NPC), radiotherapy is the primary treatment. However, complications occur after radiation to the nasopharynx, which could potentially affect the flying safety. Four fighter pilots with NPC were reported. With early to locally advanced NPC, they received radiotherapy with or without concurrent chemotherapy. The prescribed radiation dose was 70 Gy to the primary tumor over the nasopharynx. Before treatment, all patients presented with various degrees of hearing loss on pure tone audiometry (main frequencies of 20-45 dB at 3-4.5 kHz for affected ears). After the full course of radiotherapy, tumor regression was noticed during months to years of follow-ups. The follow-up audiometry evaluation showed gradually recovered hearing function (average improvement of 5 dB at pretreatment frequencies) in all pilots. They then returned back to the flight line on annual waiver points. Here, we conclude that fighter pilots with NPC could successfully return to the flight line after radiotherapy. However, detailed physical examinations and confirmation of adaptation to flying condition are warranted. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors have an increased risk of heart failure, ischemic heart disease, and stroke. They may benefit from prediction models that account for cardiotoxic cancer treatment exposures combined with information on traditional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes.Methods: Childhood Cancer Survivor Study participants (n = 22 643) were followed through age 50 years for incident heart failure, ischemic heart disease, and stroke. Siblings (n = 5056) served as a comparator. Participants were assessed longitudinally for hypertension, dyslipidemia, and diabetes based on self-reported prescription medication use. Half the cohort was used for discovery; the remainder for replication. Models for each outcome were created for survivors ages 20, 25, 30, and 35 years at the time of prediction (n = 12 models).Results: For discovery, risk scores based on demographic, cancer treatment, hypertension, dyslipidemia, and diabetes information achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater in 9 and 10 of the 12 models, respectively. For replication, achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater were observed in 7 and 9 of the models, respectively. Across outcomes, the most influential exposures were anthracycline chemotherapy, radiotherapy, diabetes, and hypertension. Survivors were then assigned to statistically distinct risk groups corresponding to cumulative incidences at age 50 years of each target outcome of less than 3% (moderate-risk) or approximately 10% or greater (high-risk). Cumulative incidence of all outcomes was 1% or less among siblings.Conclusions: Traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-age survivors of childhood cancer. These prediction models provide a framework on which to base future surveillance strategies and interventions. [ABSTRACT FROM AUTHOR]

Background: Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more appropriate in some trials. These new features of immunotherapy make conventional phase II trial designs, which assume a single binary endpoint that is quickly ascertainable, inefficient and dysfunctional.Methods: We propose a flexible and efficient time-to-event Bayesian optimal phase II (TOP) design. The TOP design is efficient in that it allows real-time "go/no-go" interim decision making in the presence of late-onset responses by using all available data and maximizes statistical power for detecting effective treatments. TOP is flexible in the number of interim looks and capable of handling simple and complicated endpoints under a unified framework. We conduct simulation studies to evaluate the operating characteristics of the TOP design.Results: In the considered trial settings, compared to some existing Bayesian designs, the TOP design shortens the trial duration by 4-10 months and improves the power to detect effective treatment up to 90%, with well-controlled type I errors.Conclusions: The TOP design is transparent and easy to implement, as its decision rules can be tabulated and included in the protocol prior to the conduct of the trial. The TOP design provides a flexible, efficient, and easy-to-implement method to accelerate and improve the development of immunotherapies. [ABSTRACT FROM AUTHOR]

Chemotherapy and radiation therapy are the foundations of adjuvant therapy for early-stage breast cancer. As a complication of cytotoxic regimens, breast cancer patients are at risk for therapy-related myeloid neoplasms (t-MNs). These t-MNs are commonly refractory to antileukemic therapies and result in poor patient outcomes. We previously demonstrated that somatic mutations in leukemia-related genes are present in the tumor-infiltrating leukocytes (TILeuks) of a subset of early breast cancers. Here, we performed genomic analysis of microdissected breast cancer tumor cells and TILeuks from seven breast cancer patients who subsequently developed leukemia. In four patients, mutations present in the leukemia were detected in breast cancer TILeuks. This finding suggests that TILeuks in the primary breast cancer may harbor the ancestor of the future leukemogenic clone. Additional research is warranted to ascertain whether infiltrating mutant TILeuks could constitute a biomarker for the development of t-MN and to determine the functional consequences of mutant TILeuks. [ABSTRACT FROM AUTHOR]

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: Increasingly, acute promyelocytic leukemia (APL) is treated with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). This study characterizes bone marrow findings after ATRA/ATO therapy.Methods: Bone marrow biopsies from 16 patients treated with ATRA/ATO and seven patients treated with ATRA/chemotherapy (CTX) for APL were evaluated.Results: In ATRA/ATO cases, the marrow was likely to be hypercellular (79%) with a decreased myeloid:erythroid (M:E) ratio (88%), megaloblastoid maturation of erythroid precursors (100%), erythroid atypia (75%), and increased (88%) and atypical (75%) megakaryocytes. Significant myeloid atypia was only seen in extensive residual disease. The ATRA/CTX cases were less likely to be hypercellular (38%), have a M:E ratio of 1:1 or less (0%), exhibit significant erythroid atypia (0%), or have increased (0%) or atypical (38%) megakaryocytes.Conclusions: Bone marrow biopsies from patients treated with ATO have unusual but characteristic features. Despite variability in marrow findings, clinical outcomes were uniformly favorable. [ABSTRACT FROM AUTHOR]

Background: The Wnt/β-catenin pathway is closely associated with osteosarcoma (OS) development and metastatic progression. We investigated the antitumor activity of Tegavivint, a novel β-catenin/transducin β-like protein 1 (TBL1) inhibitor, against OS employing in vitro, ex vivo, and in vivo cell line and patient-derived xenograft (PDX) models that recapitulate high risk disease.Methods: The antitumor efficacy of Tegavivint was evaluated in vitro using established OS and PDX-derived cell lines. Use of an ex vivo three-dimensional pulmonary metastasis assay assessed targeting of β-catenin activity during micro- and macrometastatic development. The in vivo activity of Tegavivint was evaluated using chemoresistant and metastatic OS PDX models. Gene and protein expression were quantified by quantitative Reverse transcription polymerase chain reaction or immunoblot analysis. Bone integrity was determined via microCT. All statistical tests were two-sided.Results: Tegavivint exhibited antiproliferative activity against OS cells in vitro and actively reduced micro- and macrometastatic development ex vivo. Multiple OS PDX tumors (n = 3), including paired patient primary and lung metastatic tumors with inherent chemoresistance, were suppressed by Tegavivint in vivo. We identified that metastatic lung OS cell lines (n = 2) exhibited increased stem cell signatures, including enhanced concomitant aldehyde dehydrogenase (ALDH1) and β-catenin expression and downstream activity, which were suppressed by Tegavivint (ALDH1: control group, mean relative mRNA expression = 1.00, 95% confidence interval [CI] = 0.68 to 1.22 vs Tegavivint group, mean = 0.011, 95% CI = 0.0012 to 0.056, P < .001; β-catenin: control group, mean relative mRNA expression = 1.00, 95% CI = 0.71 to 1.36 vs Tegavivint group, mean = 0.45, 95% CI = 0.36 to 0.52, P < .001). ALDH1high PDX-derived lung OS cells, which demonstrated enhanced metastatic potential compared with ALDHlow cells in vivo, were sensitive to Tegavivint. Toxicity studies revealed decreased bone density in male Tegavivint-treated mice (n = 4 mice per group).Conclusions: Tegavivint is a promising therapeutic agent for advanced stages of OS via its targeting of the β-catenin/ALDH1 axis. [ABSTRACT FROM AUTHOR]

Objective This case study illustrates the importance of considering English-language proficiency (ELP) when testing linguistically diverse individuals with medical conditions. Case Description Julia is a 10-year-old girl born to immigrant parents. She was primarily exposed to Spanish at home. At 4 years, she was diagnosed with medulloblastoma, had a craniotomy (gross total resection), craniospinal radiation, and 1 year of chemotherapy. Although in remission, lasting effects included ataxia, fine-and gross- motor impairment, hand-dominance switch, and mild hearing loss. Moreover, Julia's schooling was delayed until she was 6 years old. Julia has struggled academically with vocabulary, phonemic awareness, reading fluency/comprehension, and listening comprehension. At 9 years, Julia was evaluated in English only and was reported to be in the Extremely Low range of cognitive function, attributed to her medical history. Despite her history of bilingual language acquisition, Julia's ELP was not assessed and her abilities were likely underestimated. When Julia was 10 years old, a bilingual clinician conducted an evaluation to better assess Julia's cognitive ability. Her performance greatly improved when tested in Spanish (increase in scores of >1 standard deviation). Diagnostic Impressions and Outcomes Julia was diagnosed with mild neurocognitive disorder due to another medical illness. However, her performance was likely impacted by her ELP as well, which was not being addressed. Discussion In order to accurately assess bilingual children with neurocognitive deficits resulting from medical complications, ELP and acquisition should be considered. In Julia's case, her brain tumor, radiation, and chemotherapy likely disrupted her cognitive development during a critical time for language development. [ABSTRACT FROM AUTHOR]

Background: The β-lactam antibiotic piperacillin (in combination with tazobactam) is commonly chosen for empirical treatment of suspected bacterial infections. However, pharmacokinetic variability among patient populations and across ages leads to uncertainty when selecting a dosing regimen to achieve an appropriate pharmacodynamic target.Objectives: To guide dosing by establishing a population pharmacokinetic model for unbound piperacillin in febrile children receiving cancer chemotherapy, and to assess pharmacokinetic/pharmacodynamic target attainment (100% fT > 1×MIC and 50% fT > 4×MIC) and resultant exposure, across body weights.Methods: Forty-three children admitted for 89 febrile episodes contributed 482 samples to the pharmacokinetic analysis. The typical doses required for target attainment were compared for various dosing regimens, in particular prolonged infusions, across MICs and body weights.Results: A two-compartment model with inter-fever-episode variability in CL, and body weight included through allometry, described the data. A high CL of 15.4 L/h (70 kg) combined with high glomerular filtration rate (GFR) values indicated rapid elimination and hyperfiltration. The target of 50% fT > 4×MIC was achieved for an MIC of 4.0 mg/L in a typical patient with extended infusions of 2-3 (q6h) or 3-4 (q8h) h, at or below the standard adult dose (75 and 100 mg/kg/dose for q6h and q8h, respectively). Higher doses or continuous infusion were needed to achieve 100% fT > 1×MIC due to the rapid piperacillin elimination.Conclusions: The licensed dose for children with febrile neutropenia (80 mg/kg q6h as a 30 min infusion) performs poorly for attainment of fT>MIC pharmacokinetic/pharmacodynamic targets. Given the population pharmacokinetic profile, feasible dosing regimens with reasonable exposure are continuous infusion (100% fT > 1×MIC) or prolonged infusions (50% fT > 4×MIC). [ABSTRACT FROM AUTHOR]

A large body of evidence indicates that cancer survivors who have undergone chemotherapy have cognitive impairments. Substantial disagreement exists regarding which cognitive domains are impaired in this population. We suggest that is in part due to inconsistency in how neuropsychological tests are assigned to cognitive domains. The purpose of this paper is to critically analyze the meta-analytic literature on cancer-related cognitive impairments (CRCI) to quantify this inconsistency. We identified all neuropsychological tests reported in seven meta-analyses of the CRCI literature. Although effect sizes were generally negative (indicating impairment), every domain was declared to be impaired in at least one meta-analysis and unimpaired in at least one other meta-analysis. We plotted summary effect sizes from all the meta-analyses and quantified disagreement by computing the observed and ideal distributions of the one-way χ2 statistic. The actual χ2 distributions were noticeably more peaked and shifted to the left than the ideal distributions, indicating substantial disagreement among the meta-analyses in how neuropsychological tests were categorized to domains. A better understanding of the profile of impairments in CRCI is essential for developing effective remediation methods. To accomplish this goal, the research field needs to promote better agreement on how to measure specific cognitive functions. [ABSTRACT FROM AUTHOR]

We retrospectively studied outcomes in patients treated with preoperative radiochemotherapy and surgery for esophageal squamous cell cancer. We put special focus on the comparison of patients treated with 5-fluorouracil/cisplatin (‘Walsh’) or carboplatin/paclitaxel (‘CROSS’). We compared characteristics between patients treated according to ‘Walsh’ vs. ‘CROSS’. Cox regression was performed to test for an association of parameters with outcomes. Study eligibility was met by 90 patients. First, the higher age and more comorbidities of the ‘CROSS’ patients, along with a shorter intensive care/intermediate care stay, might reflect an improvement in supportive and surgical/perioperative procedures over the periods. Second, the ‘CROSS’ patients experienced more hematologic toxicity and were less likely to complete chemotherapy as per protocol. This indicates that efforts should be taken to guide patients through a toxic treatment regimen by supportive measures. Third, the negative prognostic impact of radiochemotherapy-related toxicities (i.e., dysphagia and hematologic toxicities) and the duration of the intensive care/intermediate care unit stay underlines that further optimization of treatment procedures remains an important goal. We found no differences in tumor downstaging and survival between treatment regimen. Toxicity profiles could be improved by tailoring the regimen to individual patients (e.g., careful use of the taxane-based regimen in elderly patients).

Purpose: To compare the efficacy of taxane (T) based neoadjuvant chemotherapy (NAC) with T and anthracycline (A) based NAC in different molecular types of breast cancer (BC)., Methods: We retrospectively analyzed the date of NAC for BC from 20 hospitals in China from January 2010 to December 2020, 7870 cases were enrolled. The propensity score matching was used to equalize the baseline characteristics. Pathological complete response (pCR) rate, clinical response rate and breast-conserving rate were analyzed., Results: The efficacy of 2 regimens were similar in luminal A subtype. The breast-conserving rate was higher in T-based NAC in luminal B subtype (17.9% vs. 10.2%, P = .043).The pCR (T0/isN0M0) and tpCR (T0N0M0) rates in T-based NAC were higher than those in TA-based NAC for triple-negative subtype (pCR: 34.5% vs. 25.8%, P = .041, tpCR: 26.9% vs. 17.1%, P = .008). For HER2+(HR-) subtype, the pCR, and tpCR rates were higher in T-based NAC in insufficient anti-HER2 therapy (P < .05), and those were higher in TA-based NAC in dual-target anti-HER2 therapy (pCR: 69.2% vs. 53.8%, P = .254, tpCR: 61.5% vs. 42.3%, P = .165). For HER2+(HR+) breast cancer, both pCR and tpCR rates were higher in TA group, regardless of the adequacy of anti-HER2 treatment., Conclusions: T-based NAC could replace TA-based NAC for luminal A, luminal B, and triple-negative early-stage BC, but anthracyclines cannot be abandoned in HER2+ breast cancer. The development of anthracyclines with lower adverse reactions is one of the directions for the treatment of HER2+ breast cancer., Competing Interests: Disclosure All authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Breast cancer, a multi-networking heterogeneous disease, has emerged as a serious impediment to progress in clinical oncology. Although technological advancements and emerging cancer research studies have mitigated breast cancer lethality, a precision cancer-oriented solution has not been achieved. Thus, this review will persuade the acquiescence of proteomics-based diagnostic and therapeutic options in breast cancer management. Recently, the evidence of breast cancer health surveillance through imaging proteomics, single-cell proteomics, interactomics, and post-translational modification (PTM) tracking, to construct proteome maps and proteotyping for stage-specific and sample-specific cancer subtyping have outperformed conventional ways of dealing with breast cancer by increasing diagnostic efficiency, prognostic value, and predictive response. Additionally, the paradigm shift in applied proteomics for designing a chemotherapy regimen to identify novel drug targets with minor adverse effects has been elaborated. Finally, the potential of proteomics in alleviating the occurrence of chemoresistance and enhancing reprofiled drugs' effectiveness to combat therapeutic obstacles has been discussed. Owing to the enormous potential of proteomics techniques, the clinical recognition of proteomics in breast cancer management can be achievable and therapeutic intricacies can be surmountable., (© 2023 Wiley-VCH GmbH.)

Background: Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood.Methods: Among 2053 retinoblastoma patients diagnosed during 1914-2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population.Results: Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15-29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER<15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients.Conclusion: Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past. [ABSTRACT FROM AUTHOR]

We retrospectively assessed association of stromal tumor-infiltrating lymphocytes (sTILs) with clinical outcomes and molecular variables reportedly predictive of trastuzumab-benefit in National Surgical Adjuvant Breast and Bowel Project B-31 (N = 2130). sTILs were assessed in 1581 eligible B-31 cases utilizing all available hematoxylin and eosin slides. Mean concordance between main reviewer and six other pathologists was 90.8% in 100 cases. Cox regressions were used to calculate hazard ratios (HRs). In chemotherapy and trastuzumab added to chemotherapy arms, increases in sTILs, as a semicontinuous variable (combined arms HR = 0.42, 95% confidence interval = 0.27 to 0.64, two-sided P < .001) or as lymphocyte-predominant breast cancer with more than 50% sTILs (combined arms HR = 0.65, 95% confidence interval = 0.49 to 0.86, two-sided P = .003) were statistically significantly associated with improved disease-free survival. There was no association of sTILs with trastuzumab benefit. However, higher sTILs were statistically significantly associated with higher trastuzumab benefit groups by 8-gene prediction model (two-sided P < .001). Neither PIK3CA mutations nor Fc-gamma-receptor polymorphisms were associated with sTILs. sTILs may have utility as a prognostic biomarker identifying HER2-positive early breast cancer at low recurrence risk. [ABSTRACT FROM AUTHOR]

Background: We previously showed that therapy with anti-checkpoints T-lymphocyte-associated protein 4 (anti-CTLA-4) or antiprogrammed cell death protein 1 (anti-PD-1) agents was more effective for men as compared with women. However, because the sex-dimorphism of the immune system is complex, involving multiple elements of immune responses, it is possible that women could derive larger benefit than men from strategies other than therapy with immune checkpoint inhibitors (ICIs) alone. Here we investigated whether women could derive larger benefit than men from the combination of chemotherapy and anti-PD-1 or anti-PD-L1.Methods: We performed two meta-analyses. The first included all randomized controlled trials (RCTs) testing anti-PD1 and anti-PD-L1 plus chemotherapy vs chemotherapy to assess different efficacy between men and women. The second included all RCTs of first-line systemic treatment in advanced non-small cell lung cancer testing anti-PD-1/PD-L1 given either alone or combined with chemotherapy to assess the different efficacy of these two immunotherapeutic strategies according to patients' sex. For each RCT included in the two meta-analyses, first, a trial-specific ratio of hazard ratios (HRs) was calculated from the ratio of the reported hazard ratios in men and in women; second, these trial-specific ratios of hazard ratios were combined across trials using a random-effects model to obtain a pooled hazard ratios ratio. A pooled HRs ratio estimate lower than 1 indicates a greater treatment effect in men, and higher than 1 a greater effect in women.Results: Eight RCTs were included in the first meta-analysis. The pooled overall survival hazard ratios (OS-HRs) comparing anti-PD-1/PD-L1 plus chemotherapy vs chemotherapy was 0.76 (95% confidence interval [CI] = 0.66 to 0.87) for men and 0.48 (95% CI = 0.35 to 0.67) for women. The pooled ratio of the overall survival hazard ratios reported in men vs women was 1.56 (95% CI = 1.21 to 2.01), indicating a statistically significant greater effect for women. Six RCTs were included in the second meta-analysis: three tested an anti-PD-1 alone, whereas three RCTs tested anti-PD-1/PD-L1 plus chemotherapy. The pooled overall survival hazard ratios were 0.78 (95% CI = 0.60 to 1.00) in men and 0.97 (95% CI = 0.79 to 1.19) in women for anti-PD-1 alone, compared with 0.76 (95% CI = 0.64 to 0.91) in men and 0.44 (95% CI = 0.25 to 0.76) in women for anti-PD-1/PD-L1 plus chemotherapy. The pooled ratio of overall survival hazard ratios was 0.83 (95% CI = 0.65 to 1.06) for anti-PD-1 alone, indicating a greater effect in men, and 1.70 (95% CI = 1.16 to 2.49) for anti-PD-1/PD-L1 plus chemotherapy, indicating a greater effect in women.Conclusion: Women with advanced lung cancer derived a statistically significantly larger benefit from the addition of chemotherapy to anti-PD-1/PD-L1 as compared with men. [ABSTRACT FROM AUTHOR]

Background: Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.Methods: The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.Results: Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).Conclusion: CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers. [ABSTRACT FROM AUTHOR]

The article focuses on the study to investigate the effects of trimodality therapy on the outcomes of patients with SSTs. Induction chemoradiotherapy followed by surgery is the standard treatment for superior sulcus tumours (SSTs). However, the protocols, chemotherapy agents and cycles used as well as the mode and intensity of radiotherapy vary between institutions.

Background: The objective of this study was to evaluate the efficacy and safety of gemcitabine plus cisplatin concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma.Method: Patients with NPC were randomly assigned to the gemcitabine plus cisplatin (GP) group or fluorouracil plus cisplatin (PF) group. Primary end-point was disease-free survival (DFS); secondary endpoints: overall survival, distant metastasis-free survival (DMFS), locoregional relapse-free survival, and treatment-related adverse events.Results: Seventy-six patients were prospectively enrolled and the median follow-up time was 41 months (9-61 months). Three-year DFS were similar between the GP and PF groups (73.7% vs. 60.5%, HR 0.66, 95% CI 0.30-1.44; P = 0.30). Distant metastasis was the most common failure form in PF compared with GP (P = 0.034). Three-year DMFS was significantly better in the GP group than PF group (89.5% vs. 71.1%, P = 0.045). Grade 3-4 gastrointestinal toxicities (vomiting and diarrhea) were significantly more common in the PF group; grade 3-4 neutropenia and thrombocytopenia were more common in the GP group.Conclusion: Gemcitabine plus cisplatin could be used as an alternative regimen in CCRT for nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background: An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC.Methods: This population-based cohort study included female patients diagnosed with first invasive BC between 2003 and 2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC and CBC subtypes.Results: Of 83 144 BC patients, 2816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI] = 3.7% to 4.0%). Overall, adjuvant chemotherapy (HR = 0.70, 95% CI = 0.62 to 0.80), endocrine therapy (HR = 0.46, 95% CI = 0.41 to 0.52), and trastuzumab with chemotherapy (HR = 0.57, 95% CI = 0.45 to 0.73) were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR = 0.48, 95% CI = 0.36 to 0.62) and aromatase inhibitors (HR = 0.32, 95% CI = 0.23 to 0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of estrogen receptor (ER)-positive CBC (HR = 0.41, 95% CI = 0.36 to 0.47) but not ER-negative CBC (HR = 1.32, 95% CI = 0.90 to 1.93) compared with no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up (HR = 2.84, 95% CI = 1.62 to 4.99) compared with patients not receiving chemotherapy for ER-negative first BC.Conclusion: Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduce CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with a distinctive regional and racial prevalence. It is associated with Epstein-Barr virus infection and has a high propensity for regional and distant metastases, while it is very sensitive to radiation and chemotherapy. A common feature of Epstein-Barr virus-positive NPC is the dense infiltration of lymphocytes in the tumor stroma and positive programmed death-ligand 1 expression in tumor cells, making it an attractive target for immunotherapy, especially immune checkpoint inhibitors. As new immunotherapeutic agents are being rapidly adopted in many cancers, including head and neck cancer, the National Cancer Institute sponsored a clinical trial planning meeting to identify opportunities for developing phase II and III trials testing immunotherapy in different stages of NPC. The meeting started with the summary of the biology of the disease, current standards of care, and evidence of immunotherapy in this cancer. Three subcommittees were tasked to develop clinical trials: loco regionally advanced, nonmetastatic NPC; widely metastatic NPC; and either local recurrence after initial treatment or presenting with oligometastatic disease. This article summarizes the proceedings of this clinical trial planning meeting and provides a road map for future trials incorporating immune checkpoint inhibitors for therapeutic management of NPC. This road map, though specific for NPC, may also be applicable to other virally driven cancers that have similar ability to evade the host's immune system. [ABSTRACT FROM AUTHOR]

Primary squamous cell carcinoma of the breast is a rare tumor. The prognosis is poor, and hence there is a clinical trend to offer multi-modal treatment options of surgery, chemotherapy, and radiation therapy. There is no consensus on treatment options due to the paucity of available data. We are reporting the case of a 68-year-old lady who presented with a right breast mass. Upon core biopsy and further workup, she was noted to have primary squamous cell carcinoma of the breast. She was successfully treated with surgical therapy alone without disease recurrence at 36 months. Primary squamous cell carcinoma of the breast can be treated successfully with surgical therapy alone. The role of adjuvant chemotherapy, radiation therapy, and anti-estrogen therapy should be questioned as these modalities can lead to significant treatment-related morbidities and might not be contributing to disease-free interval or overall survival from this unusual tumor subtype. [ABSTRACT FROM AUTHOR]

Background: Infections with antibiotic-resistant pathogens in cancer patients are a leading cause of mortality. Cancer patients are treated with compounds that can damage bacterial DNA, potentially triggering the SOS response, which in turn enhances the bacterial mutation rate. Antibiotic resistance readily occurs after mutation of bacterial core genes. Thus, we tested whether cancer chemotherapy drugs enhance the emergence of resistant mutants in commensal bacteria.Methods: Induction of the SOS response was tested after the incubation of Escherichia coli biosensors with 39 chemotherapeutic drugs at therapeutic concentrations. The mutation frequency was assessed after induction with the SOS-inducing chemotherapeutic drugs. We then tested the ability of the three most highly inducing drugs to drive the emergence of resistant mutants of major bacterial pathogens to first-line antibiotics.Results: Ten chemotherapeutic drugs activated the SOS response. Among them, eight accelerated the evolution of the major commensal E. coli, mostly through activation of the SOS response, with dacarbazine, azacitidine and streptozotocin enhancing the mutation rate 21.3-fold (P < 0.001), 101.7-fold (P = 0.01) and 1158.7-fold (P = 0.02), respectively. These three compounds also spurred the emergence of imipenem-resistant Pseudomonas aeruginosa (up to 6.21-fold; P = 0.05), ciprofloxacin-resistant Staphylococcus aureus (up to 57.72-fold; P = 0.016) and cefotaxime-resistant Enterobacteria cloacae (up to 4.57-fold; P = 0.018).Conclusions: Our results suggest that chemotherapy could accelerate evolution of the microbiota and drive the emergence of antibiotic-resistant mutants from bacterial commensals in patients. This reveals an additional level of complexity of the interactions between cancer, chemotherapy and the gut microbiota. [ABSTRACT FROM AUTHOR]

Study Question: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy?Summary Answer: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation.What Is Known Already: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC.Study Design, Size, Duration: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015.Participants/materials, Setting, Methods: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density).Main Results and Role Of Chance: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients.Limitations, Reasons For Caution: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance.Wider Implications Of the Findings: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised.Study Funding/competing Interest(s): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report.Trial Registration Number: NCT02184806. [ABSTRACT FROM AUTHOR]