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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]

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]

Background: Internal mammary lymph nodes (IMNs) are a potential site of metastasis for breast cancer. Targeting IMNs as part of a comprehensive regional nodal irradiation comes at the cost of higher unwanted doses to critical nearby organs at risk. Thus, the efficacy and safety of different radiotherapy techniques for the coverage of this area remain elusive. Objectives: We present a dosimetric comparison between partially wide tangents (PWT) and direct photon/electron (P/E) portals in terms of target volume coverage and normal tissue sparing. Methods: Patients with left-sided breast cancer, who were referred to our clinic for post-lumpectomy or post-mastectomy radio-therapy, underwent computed tomography (CT) simulation. The left breast and IMNs, heart, lung, right breast, and esophagus were contoured. Dosimetric comparisons were based on dose-volume histograms (DVHs) generated for all of the aforementioned organs. A subgroup analysis was also performed based on patients' type of surgical treatment. Results: A total of 30 patients (10 with breast conserving surgery and 20 with modified radical mastectomy) were included. The P/E plan provided a higher coverage of the left breast (P-value of CTV V105%: < 0.001) and IMNs with a P-value of 0.087 regarding the mean dose received by IMNs, and also less volume of the heart (P-value of Heart V30Gy: 0.021), and lungs (P-value of Lung V20Gy: 0.003) were irradiated. However, these advantages came at the cost of a higher dose to the esophagus and right breast and more hotspots compared to the PWT technique. Conclusions: The P/E technique had advantages regarding target volume coverage and toxicity regardless of the type of surgery. Based on the results of this study, overall, the P/E portal is superior to the PWT for radiotherapy of breast cancer with internal mammary node inclusion. However, the appropriate treatment plan should be decided on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Purpose: Peripheral neuropathy is a dose-limiting adverse effect of oxaliplatin. The aim of this study was to evaluate the efficacy and safety of duloxetine in the prevention of oxaliplatin-induced peripheral neuropathy (OIPN). Method: Cancer patients receiving oxaliplatin based chemotherapy were randomized into two arms. Duloxetine 60 mg capsule was given in the first 14 days of each chemotherapy cycle to one arm and placebo was similarly given to another. We compared the two arms based on the incidence of neuropathy and the results of the nerve conduction study (NCS). Grade of complained neuropathy was recorded according to Common Terminology Criteria for Adverse Events (CTCAE). Results: Thirty-two patients mostly rectal cancer (90.6%) were randomized to duloxetine and placebo arms. Highest grade of neuropathy in each cycle was not significantly different between the two groups. Six weeks after treatment incidence of neuropathy of any grade was 52.9 in duloxetine arm compared to 76.9% in placebo arm (P: 0.26). Patients in the duloxetine arm had a lower percentage of chemotherapy cycles (mean) in which they reported distal paresthesia (51% vs. 84%, P = 0.01) and throat discomfort (37% vs. 69%, P = 0.01). Results of NCS were mostly comparable between the two arms except for the velocity in two of the examined nerve which was significantly higher in duloxetine group. Duloxetine was safe and well-tolerated. Conclusion: Although a definite conclusion might be difficult to draw but administering duloxetine for 14 days in each chemotherapy cycle could not decrease the incidence of acute OIPN based on CTCAE grading system. [ABSTRACT FROM AUTHOR]

Background and Objectives: The non-surgical treatment outcome of gastroesophageal junction (GEJ) adenocarcinoma remains to be defined. We aimed to assess the outcomes of definitive chemoradiation (CRT) of GEJ tumors. Methods: This retrospective cohort study was entirely carried out in the radiation oncology ward of Cancer Institute of Iran. We included patients with adenocarcinoma histology whose tumors had involved the gastro-esophageal junction and underwent chemoradiotherapy without surgery. In the final analysis, we evaluated 50 patients with non-metastatic adenocarcinoma of GEJ (Siewert's type I and II) from 2008 to 2017. The primary outcome was overall survival; secondary outcomes were progression-free survival and local and distal metastasis. Results: The reasons for not undergoing surgery in order of frequency from highest to lowest were patient refusal or medical unfitness for surgery, tumor unresectability or progress at the time of operation and incident metastasis in pre-op restaging, and. The 1-year, 2-year, and 3-year overall survival rates were 53%, 26%, and 12%, respectively. The 1-year, 2-year, and 3-year progression-free survival rates were 44%, 18%, and 10%, respectively. In the multivariate analysis, the only independent predictor of survival was a distant failure (P=0.031). Conclusion: Although the outcomes of non-surgical treatments are disappointing in GEJ adenocarcinomas, a few patients may experience long-term survival using definitive CRT. This option should be discussed with all patients who are not candidates for surgery. [ABSTRACT FROM AUTHOR]

Background & Objective: Iran is located in the esophageal cancer geographical belt. As multiple genetic alterations are responsible for the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role and frequency of HER2 expression, MMR deficiency, and PI3KCA mutation are not well defined. Methods: We carried out HER2/neu expression, dMMR/MSI high, and PI3KCA mutation analysis in specimens of patients with ESCC. We accessed archival tissue blocks related to specimens of 68 ESCC cases at the time of surgery following neoadjuvant chemoradiation. These patients underwent surgery during 2013-2018 at the Cancer Institute of Iran affiliated with the Tehran University of Medical Sciences in Tehran. Results: None of the patients showed HER2 expression, dMMR/MSI high, or PI3K mutations. Conclusion: dMMR/MSI-H and PI3KCA mutation and HER2 expression may not be reliable andfrequent targets for systemic therapy in patients with esophageal SCC. [ABSTRACT FROM AUTHOR]

The main prostate cancer (PCa) treatments include surgery or radiotherapy (with or without ADT). However, none of the suggested treatments eliminates the risk of lymph node metastases. Conventional imaging methods, including MRI and CT scanning, are not sensitive enough for the diagnosis of lymph node metastases; however, the novel imaging method, PSMA PET/CT scanning, has provided valuable information about the pelvic LN involvement in patients with recurrent PCa (RPCa) after radical prostatectomy. The high sensitivity and negative predictive value enable accurate N staging in PCa patients. In this narrative review, we summarize the evidence on the treatment and extent of radiation in prostate-only or whole-pelvis radiation in patients with positive and negative LN involvement on PSMA PET/CT scans. [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]