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Abstract Background Patients with unresectable recurrent rectal cancer (RRC) or colorectal cancer (CRC) with liver metastases, refractory to at least two lines of traditional systemic therapy, may receive third line intraarterial chemotherapy (IC) and targeted therapy (TT) using drugs selected by chemosensitivity and tumor gene expression analyses of liquid biopsy-derived circulating tumor cells (CTCs). Methods In this retrospective study, 36 patients with refractory unresectable RRC or refractory unresectable CRC liver metastases were submitted for IC and TT with agents selected by precision oncotherapy chemosensitivity assays performed on liquid biopsy-derived CTCs, transiently cultured in vitro, and by tumor gene expression in the same CTC population, as a ratio to tumor gene expression in peripheral mononuclear blood cells (PMBCs) from the same individual. The endpoint was to evaluate the predictive accuracy of a specific liquid biopsy precision oncotherapy CTC purification and in vitro culture methodology for a positive RECIST 1.1 response to the therapy selected. Results Our analyses resulted in evaluations of 94.12% (95% CI 0.71–0.99) for sensitivity, 5.26% (95% CI 0.01–0.26) for specificity, a predictive value of 47.06% (95% CI 0.29–0.65) for a positive response, a predictive value of 50% (95% CI 0.01–0.98) for a negative response, with an overall calculated predictive accuracy of 47.22% (95% CI 0.30–0.64). Conclusions This is the first reported estimation of predictive accuracy derived from combining chemosensitivity and tumor gene expression analyses on liquid biopsy-derived CTCs, transiently cultured in vitro which, despite limitations, represents a baseline and benchmark which we envisage will be improve upon by methodological and technological advances and future clinical trials.

Abstract Background Neuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1. Case presentation A 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months. Discussion and conclusions This case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.

Abstract Background This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. Methods 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. Results PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. Conclusions Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT – Napoli – 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it