Search

BACKGROUND Rectum-preservation for locally advanced rectal cancer has been proposed as an alternative to total mesorectal excision (TME) in patients with major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The purpose of this study was to report on the short-term outcomes of ReSARCh (Rectal Sparing Approach after preoperative Radio- and/or Chemotherapy) trial, which is a prospective, multicenter, observational trial that investigated the role of transanal local excision (LE) and watch-and-wait (WW) as integrated approaches after neoadjuvant therapy for rectal cancer. METHODS Patients with mid-low rectal cancer who achieved mCR or cCR after neoadjuvant therapy and were fit for major surgery were enrolled. Clinical response was evaluated at 8 and 12 weeks after completion of chemoradiotherapy. Treatment approach, incidence, and reasons for subsequent TME were recorded. RESULTS From 2016 to 2019, 160 patients were enrolled; mCR or cCR at 12 weeks was achieved in 64 and 96 of patients, respectively. Overall, 98 patients were managed with LE and 62 with WW. In the LE group, Clavien-Dindo 3+ complications occurred in three patients. The rate of cCR increased from 8- to 12-week restaging. Thirty-three (94.3%) of 35 patients with cCR had ypT0-1 tumor. At a median 24 months follow-up, a tumor regrowth was found in 15 (24.2%) patients undergoing WW. CONCLUSIONS LE for patients achieving cCR or mCR is safe. A 12-week interval from chemoradiotherapy completion to LE is correlated with an increased cCR rate. The risk of ypT > is reduced when LE is performed after cCR.

Extending the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery may enhance tumor response in patients with locally advanced rectal cancer. However, data on the association of delaying surgery with long-term outcome in patients who had a minor or poor response are lacking.To assess a large series of patients who had minor or no tumor response to CRT and the association of shorter or longer waiting times between CRT and surgery with short- and long-term outcomes.This is a multicenter retrospective cohort study. Data from 1701 consecutive patients with rectal cancer treated in 12 Italian referral centers were analyzed for colorectal surgery between January 2000 and December 2014. Patients with a minor or null tumor response (ypT stage of 2 to 3 or ypN positive) stage greater than 0 to neoadjuvant CRT were selected for the study. The data were analyzed between March and July 2020.Patients who had a minor or null tumor response were divided into 2 groups according to the wait time between neoadjuvant therapy end and surgery. Differences in surgical and oncological outcomes between these 2 groups were explored.The primary outcomes were overall and disease-free survival between the 2 groups.Of a total of 1064 patients, 654 (61.5%) were male, and the median (IQR) age was 64 (55-71) years. A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). A longer waiting time before surgery was associated with worse 5- and 10-year overall survival rates (67.6% [95% CI, 63.1%-71.7%] vs 80.3% [95% CI, 76.5%-83.6%] at 5 years; 40.1% [95% CI, 33.5%-46.5%] vs 57.8% [95% CI, 52.1%-63.0%] at 10 years; P .001). Also, delayed surgery was associated with worse 5- and 10-year disease-free survival (59.6% [95% CI, 54.9%-63.9%] vs 72.0% [95% CI, 67.9%-75.7%] at 5 years; 36.2% [95% CI, 29.9%-42.4%] vs 53.9% [95% CI, 48.5%-59.1%] at 10 years; P .001). At multivariate analysis, a longer waiting time was associated with an augmented risk of death (hazard ratio, 1.84; 95% CI, 1.50-2.26; P .001) and death/recurrence (hazard ratio, 1.69; 95% CI, 1.39-2.04; P .001).In this cohort study, a longer interval before surgery after completing neoadjuvant CRT was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative CRT. Based on these findings, patients who do not respond well to CRT should be identified early after the end of CRT and undergo surgery without delay.

Background: The reorganization of oncologic follow-up was crucial to maintain oncologic care and reduce patient exposure during SARS-CoV-2 pandemic Methods: Patients scheduled for follow-up oncologic visits during the lockdown period (March 9th - May 4th 2020) were included in a program of telematic follow-up (TFU) developed at the Medical Oncology Unit of Sant’Andrea and San Bartolomeo Hospital in La Spezia, Italy Eligibility for TFU was determined through a pre-screening of medical charts based on tumor type, risk of relapse, geographic accessibility and DFS Pre-calls were made by skilled nurses to assess pts’ availability for next-day phone call and to assess availability of laboratory test and imaging results A TFU form was conceived to collect pts’ clinical history, symptoms, body weight, ongoing medical therapies, DFS, blood tests and imaging results (from Hospital imaging repository or acquired in the pre-call) Pts without signs/symptoms of relapse were scheduled for the next follow-up visit and the filled-in TFU form was attached to the clinical chart When a suspected disease relapse was found, an ambulatory visit was performed Results: There were 547 pts previously scheduled for in-hospital follow-up visit between March 9th and May 4th, 2020 82 of 547 pts (15%) were considered not eligible for TFU according to the pre-screening assessment 465 pts out of 547 (85%) were included in the TFU program All these pts accepted calls with a compliance rate of 100% The median age was 73 years (34-95);152 male (33%) and 313 female (67%) The distribution by tumor type was: 179 breast cancer (38%), 86 colorectal (18%), 55 urinary tract (12%), 39 melanoma and skin (9%), 31 gynecologic (6%), 26 lung cancer(6%), 16 GEP (3%), 15 head and neck (3%), and 18 other tumors (4%) Ten patients with signs/symptoms of tumor recurrence were detected at TFU: 1 had clinical symptoms, 3 abnormal blood tests and 6 suspicious radiological findings These patients were called for live visit and tumor relapse/progression was confirmed in 10 out of 10 cases Medical or surgical treatment was started, or planned to start, in all 10 patients Conclusions: TFU proved to be feasible with an eligibility rate of 85% and 100% patients’ compliance The detection rate for tumor recurrence was 2 1% Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Background: Cancer patients are more susceptible to infections and potentially at higher risk to develop COVID-19 Tumor type and antitumor treatment may also affect both the susceptibility to and the severity of SARS COV-2 Methods: To analyze the distribution of patients who developed COVID-19 during active antineoplastic therapy and the related clinical course by tumor type, stage and class of oncologic treatment (chemo, immune, biologic, other) a multicenter, retro-prospective, observational study was proposed to the Hospital Medical Oncologic Units of the National Health Service in Italy (168 centers of the Collegio Italiano dei Primari Oncologi Medici Ospedalieri -CIPOMO) Data were collected on demographics, tumor characteristics, treatment setting, type of ongoing anti-cancer therapy and COVID-19 clinical course (phenotype, hospitalization, therapy, duration and outcome) Eligibility required a positive COVID-19 molecular test before May 4th, 2020 and at least 1 course of antitumor therapy delivered after January 15th Results: At the present analysis data are available for 116 of 168 centers (7 declined, 28 pending, 17 data awaited) 64 of 116 centers (55%) had COVID-19 positive cases (cases /center: median 3, range 1-40) At these 64 centers, 283 positive cases (males 158, 55 9% - females 125, 44 1%;median age 67 years, range 28-89) were observed among a total population of 40894 patients receiving active treatment between January 15 and May 4 2020 65 of 283 (23%) had cardiovascular comorbidities and 7 (2%) pre-existent pulmonary disease 239/283 patients (84 4%) were receiving treatment for metastatic disease and 44 (15 6%) in the adjuvant setting Breast, lung, colon and prostate cancer were the main tumor types accounting for 61 % of cases Conclusions: The occurrence of COVID-19 among cancer patients receiving active antitumor treatment appears to reflect tumor epidemiology Full analysis of the distribution of COVID-19 occurrence and clinical course by tumor type, stage and oncologic treatment will be presented Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Background: The standard approach for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). After nCRT 20% of patients achieve a clinical complete response (pCR) and could be treated with a non-operative management (NOM). Methods: The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on rectal cancer applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach addressing the following question: Should NOM vs. TME be used for patients with rectal cancer with clinical complete response after nCRT? Five outcomes were identified: disease-free survival (DFS), mortality, local recurrence, colostomy rate, and functional outcomes. Results: Nine studies were included in the analysis. A higher risk of disease recurrence was observed in the NOM group compared to the TME group (RR = 1.69, 95% CI 1.08, 2.64) on the other hand, we observed a slightly positive but not significant effect on mortality of NOM (RR = 0.82, 95% CI 0.46, 1.45). Patients in the NOM group were more likely to experience local recurrence (RR = 5.37, 95% CI 2.56, 11.27) and patients in the TME group were more likely to have a permanent colostomy (RR = 0.15, 95% CI 0.08, 0.29). Only one study evaluated functional outcomes. The overall certainty of evidence was rated as very low. Conclusions: NOM was found to correlate with a higher risk of local recurrence which did not translate in worse OS and a lower colostomy rate. Due to the paucity of evidences, no recommendations are possible. NOM remains an experimental treatment; thus, patients managed with NOM should be enrolled in clinical trials with a dedicated follow-up schedule.

Rectum-sparing approaches appear to be appropriate in rectal cancer patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The aim of the present study is to evaluate the effectiveness of rectum-sparing approaches at 2 years after the completion of neoadjuvant treatment. Patients with rectal adenocarcinoma eligible to receive neoadjuvant therapy will be prospectively enrolled. Patients will be restaged 7–8 weeks after the completion of neoadjuvant therapy and those with mCR (defined as absence of mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with mCR will undergo local excision, while patients with cCR will either undergo local excision or watch and wait policy. The main end point of the study is to determine the percentage of rectum preservation at 2 years in the enrolled patients. This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIVþ) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30%e40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5%e8% at onset, and rates of metastatic progression after primary treatment between 10 and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16e18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80%e90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer. 2014 Elsevier Ltd. All rights reserved.

The aim of this phase II study was to assess the activity of panitumumab in combination with oxaliplatin, 5-fluorouracil, and external radiotherapy (RT) as preoperative treatment in locally advanced rectal cancer patients.Patients had rectal adenocarcinoma, cT3N+ or cT4N-/+ stage, located12 cm from the anal margin. Panitumumab was administered before the start of chemo-RT, and every 2 weeks in combination with 5-fluorouracil-oxaliplatin with concurrent RT. Rectal surgery was carried out 7-8 weeks after the end of neoadjuvant treatment. The primary end point was a pathological complete response rate of 25%.Sixty patients were enrolled from February 2007 to October 2009. Fifty-five (91.7%) patients underwent surgery. Rate of pathological complete response was 21.1% (95% confidence interval 10.4% to 31.6%). Pathological downstaging occurred in 33 of 57 (57.9%) patients. Grade 3-4 toxicity during neoadjuvant treatment was diarrhea (38.9%), cutaneous reactions (18.6%), nausea (5.1%), asthenia (3.4%), anorexia (3.4%), and neutropenia (1.7%). One toxic death was observed for diarrhea.In our study, the primary end point is not reached and panitumumab combination treatment was associated with high incidence of grade 3-4 diarrhea. The higher pathological complete response rate in comparison with the results of previous neoadjuvant rectal cancer trials with anti-epidermal growth factor receptor monoclonal antibodies supports further studies necessary to understand the possibility of optimal regimens and sequences with chemo-RT.

Between February 1991 and July 1992, 79 previously untreated patients with metastatic colorectal carcinoma were enrolled in a phase II study of combined 5-fluorouracil (5-FU) and l-folinic acid (FA). 5-FU 370 mg/m2/day was administered for 5 consecutive days as an intravenous (i.v.) bolus injection preceded by l-FA 100 mg/m2/day with the same administration modality. Treatment was given every 4 weeks until progression. 79 patients were evaluable for toxicity and 64 for response. 2 patients (3%) achieved a complete remission and 8 (12.5%) a partial remission, 33 (52%) had stable disease and 21 patients (33%) had progressive disease. Median duration of remission was 32.5 weeks and median survival for all evaluable patients was 64.5 weeks. Substantial to severe side-effects occurred in 39% of patients. Dose-limiting toxicity (grade 3-4) was mainly diarrhoea (18%) and mucositis (15%). Nausea/vomiting, cutaneous toxicity, leucopenia, alopecia and conjunctivitis of grade 3-4 occurred respectively in 6, 4, 2.5, 1 and 1% of cases. Toxicity appeared to be substantially similar to that characteristic of combined 5-FU and the chiral mixture of d,l-FA. Efficacy was within the range of that observed with the 5-FU/d,l-FA combination, although at the lower level.

ERYTHROCYTES HAVE been proposed in animal models as carriers of cytotoxic drugs or as bioreactors converting prodrugs to active drugs [ 1,2]. Doxorubicin has been encapsulated in human and animal erythrocytes [3-71. Treatment of the doxorubicin-loaded erythrocytes with glutaraldehyde, a bifunctional reagent, prevented the fast efflux of doxorubicin from the cells and produced their specific targeting to the liver of mice and dogs [4-71. The present research aimed to extend these experimental studies to the clinic. A 51-year-old male had a colorectal carcinoma, massively metastatic to the liver (60% tumour involvement). The primary tumour was removed surgically and, at the time our study started, the disease was confined to the liver and slowly progressing. The patietit had an ECOG performance status of 2. He had previously failed three lines of chemotherapy (5fluorouracil, fotemustine, mitomycin), either systemic or locoregional, through a Port-a-cath implanted in the hepatic artery at the time of surgery. Informed consent was obtained from the patient. Freshly drawn erythrocytes were loaded with doxorubicin by simple diffusion [6]; the yield of encapsulation of the drug was 2 mg/ml of packed cells. Glutaraldehyde treatment (0.15% and 0.30% final concentration) was performed after encapsulation of doxorubicin [6]. This treatment substantially reduced the rate of doxorubicin efflux in vitro (more than 70% of the drug retained after 210 min at 37°C). For in viva distribution studies erythrocytes were labeled with 99mTc [8] prior to encapsulation. All manipulations were performed under sterile pyrogen-free conditions. Figure 1 shows the time-radioactivity curves over the regions of liver and heart, after administration through hepatic artery of 99mTc labeled native (a) and unloaded GA treated (b) erythrocytes. Unlike the native cells, showing a rapid transit from the liver to systemic circulation (a), the glutaraldehyde treated erythrocytes were almost completely retained by the liver (b), up to 24 hours after injection (not shown). No accumulation of