Background: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. Methods: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. Discussion: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. Trial registration: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

Background Small cell carcinoma (SCC) is a neuroendocrine tumor that usually originates in the lungs but can also arise from extrapulmonary sites. Extrapulmonary small cell carcinomas (EPSCCs) are aggressive and rare, with limited data guiding their management. This case report contributes to the literature by presenting the diagnosis and treatment of primary peritoneal SCC. Case presentation This case describes a 69-year-old man who presented with abdominal distension and pain, raising concerns for metastasis. He had a history of prostate cancer treated with radical prostatectomy and pelvic lymph node dissection. Biopsy and imaging revealed metastatic SCC involving the peritoneum and omentum. A diagnosis of primary peritoneal SCC or SCC of unknown primary origin was made due to the absence of a detectable primary tumor in typical sites. The patient underwent three separate courses of carboplatin/etoposide chemotherapy (6 cycles each), with each course resulting in significant disease regression and symptom relief. Recurrence was managed effectively with repeated chemotherapy cycles, but long-term follow-up showed the need for continued treatment to maintain disease control and quality of life. Conclusion This case underscores the importance of a multidisciplinary approach and patient-centered care in managing rare cancers like primary peritoneal SCC. Further research is essential to clarify its molecular characteristics and improve therapeutic options. Graphical abstract