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Aim: To apply extended ctDNA-based RAS genotyping to clinical criteria for improving the selection of patients eligible for anti-EGFR-based rechallenge in a real-world setting., Methods: ctDNA testing was prospectively applied to RASwt mCRC progressed after a first-line anti-EGFR-containing regimen and at least one other line. The primary endpoint was the objective response rate., Results: Among ten enrolled patients, the anti-EGFR rechallenge resulted in an objective response rate and disease control rate of 70% and 90%. The median progression-free survival was 11.3 months and overall survival was not reached. Compared with a historical cohort retreated with anti-EGFR agents based on clinical criteria, the ctDNA-driven approach resulted in a higher chance of achieving an objective response and longer survival., Conclusions: Blood-based RASwt status may enrich metastatic colorectal cancer more likely to benefit from anti-EGFR-based rechallenge. RAS genotyping in ctDNA represents a feasible, fast, and cost-effective tool to be implemented in the clinic for advancing precision medicine.

Introduction: Mixed adenoneuroendocrine carcinoma (MANEC) is an uncommon and aggressive tumor arising throughout the entire gastrointestinal tract. Treatment options are limited, and survival is dismal with conventional therapies., Case Description: We present the case of a 66-year-old man who was diagnosed with a locally advanced MANEC of the gastroesophageal junction. He was treated with perioperative chemotherapy and total gastrectomy. After anastomotic tumor recurrence was detected, he underwent three systemic regimens, including chemoradiotherapy. The patient was then tested for mismatch repair (MMR) protein status, revealing defective expression of MLH1 and PMS2 proteins. Treatment with anti-programmed death 1 (PD-1) receptor monoclonal antibody pembrolizumab was started and radiologic response is ongoing after 11 months. Clinical benefit was evident, and no immune therapy-related side effect was detected., Conclusions: To our knowledge, this is the first report of a heavily pretreated and rapidly progressing deficient MMR gastroesophageal MANEC experiencing a durable benefit from anti-PD1 treatment.

Aim: To assess patient perception toward oral chemotherapy for solid tumors, the Italian Association of Medical Oncology performed a large multi-institutional national survey., Methods: A 17-item anonymous questionnaire including 7 general and 10 investigational questions with free-text, single-choice, or multiple-choice answers was administered. Analysis of response distribution according to predefined factors was described by summary measures and conducted by χ2 test and other nonparametric tests., Results: From January to June 2010, 581 patients completed the questionnaire; data of 404 patients constituted the final study sample. Three groups could be distinguished according to treatment: IV chemotherapy (IV group, n = 313), oral chemotherapy (oral group, n = 48), or combined therapy (combined group, n = 43). Thirty-one (72%) patients in the combined group and 187 (60%) in the IV group expressed preference for oral therapy (p = 0.028). Limitations in family and work commitment were more frequently perceived by patients on IV than oral chemotherapy (147 (47%) vs 14 (29%) patients, p<0.05, and 134 (43%) vs 11 (23%) patients, p<0.05). A total of 134 (43%) patients on IV chemotherapy versus 15 (31%) patients in the oral group did not point out any limitation for number of tablets per day (p = 0.004)., Conclusions: We observed a propensity from the patient perspective in favor of oral chemotherapy that was considered to have a lower impact on family and work commitments than IV chemotherapy. The treatment that patients were taking when the questionnaire was administered likely influenced their perception and related results.

Aims and Background: "Augmented reality" is a technique to create a composite view by augmenting the real intervention field, visualized by the doctor, with additional information coming from a virtual volume generated using computed tomography (CT), magnetic resonance or ultrasound images previously acquired from the same patient. In the present study we verified the accuracy and validated the clinical use of an augmented reality navigation system produced to perform percutaneous CT-guided lung biopsies., Methods: One hundred and eighty consecutive patients with solitary parenchymal lung lesions, enrolled using a nonrandom enrollment system, underwent percutaneous CT-guided aspiration and core biopsy using a traditional technique (group C, 90 patients) and navigation system assistance (group S, 90 patients). For each patient we recorded the largest lesion diameter, procedure time, overall number of CT scans, radiation dose, and complications. The entire experimental project was evaluated and approved by the local institutional review board (ethics committee)., Results: Each procedure was concluded successfully and a pathological diagnosis was reached in 96% of cases in group S and 90% of cases in group C. Procedure time, overall number of CT scans and incident x-ray radiation dose (CTDIvol) were significantly reduced in navigation system-assisted procedures (P <0.001; z = 5.64) compared with traditional CT-guided procedures. The percentage of procedural complications was 14% in group S and 17% in group C., Conclusion: The augmented reality navigation system used in this study was a highly safe, technically reliable and effective support tool in percutaneous CT-guided lung biopsy, allowing to shorten the procedure time and reduce the incident x-ray radiation dose to patients and the rate of insufficient specimens. Furthermore, it has the potential to increase the number of procedures executed in the allocated time without increasing the number of complications.

In this report we describe the case of a young woman with familial adenomatous polyposis who developed metastatic rectal cancer during pregnancy. At diagnosis, we decided to perform a transabdominal laparoscopic adrenalectomy, because of the high risk of bowel obstruction, and to define the origin of the adrenal gland lesion, suspected to be primary on the basis of imaging results. The histological specimen showed a collision tumor between an adrenal metastasis of a rectal tumor and a primary adrenal gland carcinosarcoma. The peculiarity of the case is due not only to its clinical presentation during pregnancy, but also to the presence of this uncommon adrenal collision tumor. A particular challenge for the clinician is to define the priority between these two tumors: the presence of two distinct and colliding aggressive neoplasms poses a problem in the choice of the best therapeutic approach, also given the impossibility to biopsy all metastatic sites. However, we decided to treat the patient as having a metastatic rectal cancer, because we had a solid histological confirmation of metastases.

Background: To analyze early results of a single institution's experience using neo-adjuvant chemoradiotherapy in locally advanced, ultrasound-staged rectal cancer., Patients and Methods: Since 1998, 67 consecutive patients (36 males and 31 females; mean age, 59.5) have received preoperative combined treatment for T3 or T4 rectal cancer. All patients were staged by endorectal ultrasound and computed tomography, and all had a pathology-demonstrated invasive adenocarcinoma of the rectum. Patients were treated preoperatively with concomitant radiochemotherapy: pelvic irradiation (50 Gy in 25 fractions) and protracted-venous-infusion 5-fluorouracil (225 mg/m2/d, 7 days per week). Patients were restaged within 4 weeks, then submitted to surgery within 6-7 weeks after the end of therapy. Adjuvant postoperative chemotherapy with 5-fluorouracil plus folinic acid--the "de Gramont" schedule--for 24 weeks was purposed to all patients., Results: Radiotherapy was completed in all cases; only one patient required suspension of the treatment for grade 4 toxicity (diarrhea). Instead, chemotherapy was interrupted in 3 cases (2 for central venous catheter thrombosis and 1 for grade IV diarrhea). Sixty-six patients underwent surgical resection (1 patient died before surgical treatment). Radical surgery was performed in 94%, and 46% of the 26 patients with distal rectal cancer had a conservative sphincter-sparing surgery. A complete pathologic response (defined as no evidence of viable tumor cells) was obtained in 22%. At a median follow-up of 17 months, distant metastases have been observed in 10 patients, and 3 of them developed a local recurrence. The actuarial estimations of 4-year overall survival, disease-free survival, local and distant control are 79%, 61%, 94% and 61%, respectively., Conclusions: Preoperative chemoradiotherapy seems to be an effective and well-tolerated treatment with a low complication rate. The high percentage of down-staging and sphincter sparing, also in distal rectal cancer, shows the efficacy of the treatment, which could significantly influence the incidence of relapses and quality of life.

Aims and Background: To determine the efficacy and safety of the FOLFOX 2 regimen in patients with pretreated advanced colorectal cancer., Methods: In this single-arm phase II study, 28 patients with heavily pretreated advanced colorectal cancer received the following drug combination: oxaliplatin (100 mg/m2 for 2 hrs on day 1), folinic acid (250 mg/m2 for 2 hrs on day 1) and 5-flluorouracil (1500 mg/m2 for 22 hrs continuous infusion on days 1 and 2) every 2 weeks (one cycle). The treatment was continued until unacceptable toxicity occurred or at most for 10 cycles., Results: Nine patients (32%) had a partial response and 5 (18%) stable disease, with a median duration of tumor control of 24 weeks (range, 8-44). The median survival of patients with a partial response or stable disease was 32 weeks (range, 12-52), whereas the median overall survival was 32 weeks (range, 8-72). A clinical benefit was achieved in 32% (9/21) of the patients. Severe (grade 3-4) non-hematological toxicity included diarrhea (1 patient), nausea/vomiting (7%) and peripheral neuropathy (1 patient). Severe hematological toxicities were rare (4%)., Conclusions: Our phase II study confirmed the therapeutic effectiveness and safety of the FOLFOX 2 regimen in pretreated advanced colorectal cancer patients.

The "Misura" project is a retrospective survey, with the aim to evaluate how 5FU is used in the treatment of colorectal cancer in clinical practice in Italian oncology departments. Twenty-four centers participated. Patients seen in the second half of 1998 with colorectal cancer and treated with 5FU were analyzed. Observed patients were 664, 45.9% of patients presented metastatic disease. Biochemical modulation with folinic acid and bolus 5FU was the most used schedule (59%). The De Gramont (LV 5FU2) regimen, alone or with other cytotoxic drugs, was the second most chosen schedule (14%). The most frequent side effect observed was gastrointestinal toxicity. No hematological toxicity was demonstrated in 68.8% of patients. Cutaneous toxicity occurred in 21.1% of patients. 5FU is widely used independently by the stage of disease. In palliative treatment a variety of schedules were administered by the Italian centers, lacking a standard therapy. There are very few surveys investigating oncology clinical practice. A larger survey on this issue is auspicable.

Synchronous renal cell cancer (RCC) associated with primary neoplasms of other organs or tissues represents a rare diagnostic report during life. Recently, the widespread use of new diagnostic techniques (echography, computed tomography and magnetic resonance imaging) has permitted diagnosis of clinically silent RCC. We report 6 RCC cases occasionally diagnosed during initial staging of a primary cancer of other organs: 1 rhinopharyngeal carcinoma, 1 gastric cancer, 1 Waldenström's disease, 1 non-Hodgkin's lymphoma, 2 breast cancer, RCC was clinically silent in all patients. The diagnostic problems related to a report of a renal mass in patients with neoplastic disease at other sites and the consequent therapeutic implications are discussed.