Early prediction of histopathological response of rectal tumors after one week of preoperative radiochemotherapy using 18 F-FDG PET-CT imaging. A prospective clinical study

BACKGROUND: Preoperative radiochemotherapy (RCT) is standard in locally advanced rectal cancer (LARC). Initial data suggest that the tumor’s metabolic response, i.e. reduction of its (18) F-FDG uptake compared with the baseline, observed after two weeks of RCT, may correlate with histopathological response. This prospective study evaluated the ability of a very early metabolic response, seen after only one week of RCT, to predict the histopathological response to treatment. METHODS: Twenty patients with LARC who received standard RCT regimen followed by radical surgery participated in this study. Maximum standardized uptake value (SUV-MAX), measured by PET-CT imaging at baseline and on day 8 of RCT, and the changes in FDG uptake (ΔSUV-MAX), were compared with the histopathological response at surgery. Response was classified by tumor regression grade (TRG) and by achievement of pathological complete response (pCR). RESULTS: Absolute SUV-MAX values at both time points did not correlate with histopathological response. However, patients with pCR had a larger drop in SUV-MAX after one week of RCT (median: -35.31% vs −18.42%, p = 0.046). In contrast, TRG did not correlate with ΔSUV-MAX. The changes in FGD-uptake predicted accurately the achievement of pCR: only patients with a decrease of more than 32% in SUV-MAX had pCR while none of those whose tumors did not show any decrease in SUV-MAX had pCR. CONCLUSIONS: A decrease in ΔSUV-MAX after only one week of RCT for LARC may be able to predict the achievement of pCR in the post-RCT surgical specimen. Validation in a larger independent cohort is planned

Anal canal adenocarcinoma with a late brain metastatic lesion – a case report

Herein we present a rare case of anal canal adenocarcinoma manifesting as non-healing perianal abscess that subsequently underwent radiochemotherapy followed by abdominoperineal resection for residual disease. The patient recovered, and a year later presented with a single brain metastasis. The lesion was successfully resected, and the patient is now disease free. Resumo: Apresentamos aqui um caso raro de adenocarcinoma de canal anal que se manifesta como abscesso perianal não cicatrizado que subsequentemente foi submetido à radioquimioterapia seguida de ressecção abdominoperineal por detecção de doença residual. O paciente recuperou-se e um ano depois apresentou uma única metástase cerebral. A lesão foi ressecada com sucesso e o paciente agora está livre da doença. Keywords: Anal canal adenocarcinoma, Metastatic disease, Brain metastasis, Palavras-chave: Adenocarcinoma de canal anal, Doença metastática, Metástase cerebra

A Phase Ib/II Study Evaluating the Combination of Weekly Docetaxel and Cisplatin Together with Capecitabine and Bevacizumab in Patients with Advanced Esophago-Gastric Cancer

<div><p>Introduction</p><p>Current treatment options for advanced esophagogastric cancer (AEGC) are still unsatisfactory. The aim of this prospective phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC.</p><p>Methods</p><p>Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25–35 mg/m², days 1,8, capecitabine 1,600 mg/m² days 1–14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX (phase Ib part) and to determine the tumor response rate (phase II part).</p><p>Results</p><p>The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%), usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. The recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m² and 30 mg/m², respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). Hence, the objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. For the 17 patients treated at the MTD, the objective response rate was 41% and the disease control rate was 88%. The median overall survival (OS) for these patients was 13.9 months (range, 1.5–52.2 months) and the median progression-free survival was 7.6 months (range, 1.3–26.6 months). The 2-year OS rate reached 23.7%.</p><p>Conclusions</p><p>AVDCX was associated with a high rate of regimen related fatal adverse events and is not appropriate for further development in AEGC patients.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00845884" target="_blank">NCT00845884</a>,</p></div

CONSORT Flow Diagram.

<p>CONSORT Flow Diagram.</p

Patient characteristics (n = 22).

<p>Patient characteristics (n = 22).</p

Comparison between AVDCX, AVAGAST and DCF (V325) studies¹.

<p>Comparison between AVDCX, AVAGAST and DCF (V325) studies<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157548#t005fn002" target="_blank">¹</a>.</p

Hematological toxicities¹.

<p>Hematological toxicities<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157548#t003fn002" target="_blank">¹</a>.</p

Treatment delivery (n = 22).

<p>Treatment delivery (n = 22).</p