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The novel severe acute respiratory syndrome coronavirus-2 pandemic is a global health problem, which started to affect China by the end of 2019. In Europe, Italy has faced this novel disease entity (named novel coronavirus disease [COVID-19]) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during the pandemic.

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

Purpose A common hypothesis is that neo-adjuvant treatment in rectal cancer, is able to increase sphincter saving surgery. This review studies data relevant to this question. Study selection A total of 17 randomized trials were analysed. Results Since 1976, the rate of sphincter saving surgery increased from 20% to 75%. In none of the 17 trials it was possible to demonstrate a significant benefit of the neo-adjuvant regimens on the rate of sphincter saving surgery. There was a reduction in the risk of 5-year local recurrence partly due to these neo-adjuvant treatments. These neo-adjuvant regimens had no significant impact on the overall 5-year survival. Conclusions None of the neo-adjuvant treatments tested was able to demonstrate an increase in the rate of sphincter saving surgery. The improvement in conservative surgery is mainly due to technical changes in surgery. Organ preservation after complete clinical response appears as an interesting hypothesis to test.

Background: Oxaliplatin (OXA) significantly enhanced the antitumour activity of 5-fluorouracil (FUra) in patients with advanced colorectal cancer and displayed radiosensitising properties in preclinical studies. This study was thus performed to test the feasibility, identify the recommended doses (RDs) and explore preliminarily the clinical activity of weekly OXA and infused FUra combined with preoperative pelvic radiotherapy. Patients and methods: Forty-six patients with recurrent or locally advanced (cT3-4 and/or N+) adenocarcinomas of the mid-low rectum were treated with escalating doses of OXA (25, 35, 45, 60 mg/m2, weekly for 6 weeks) and FUra (200–225 mg/m2/day, 6-week infusion) concurrent to preoperative pelvic radiotherapy (50.4 Gy/28 fractions). The RDs for the phase II part of the study were immediately below the level resulting in dose-limiting toxicities in more than one third of the patients, or corresponded to the last planned dose level. Results: In the escalation phase, dose-limiting toxicities only occurred in one patient at the fourth level and one of six patients treated at the last planned dose level (grade III diarrhoea). OXA 60 mg/m2 and FUra 225 mg/m2/day are therefore the RDs for the regimen. Among 25 patients globally treated at these doses (phase II part), the incidence of grade III diarrhoea was 16% with no grade IV toxicity. Neurotoxicity did not exceed grade II (12%). All patients completed radiotherapy and were operated on as scheduled. Twenty-one of 25 patients had the tumour down-staged after chemoradiation with seven (28%) pathological complete responses and 12 (48%) residual tumours limited to ypT1-2N0. Conclusions: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.

In the past 15 years, the outcome for patients with metastatic colorectal cancer has substantially improved owing to the availability of new cytotoxic and biological agents along with many significant advances in molecular selection, the use of personalised therapy and locoregional treatment, a more widespread sharing of specific professional experiences (multidisciplinary teams with oncologists, surgeons, radiotherapists, radiologists, biologists and pathologists), and the adoption of patient-centred healthcare strategies. The Italian Medical Oncology Association (AIOM) has developed evidence-based recommendations to help oncologists and all professionals involved in the management of patients with metastatic colorectal cancer in their daily clinical practice.

We have recently demonstrated that bolus FUra treatments of human colon carcinoma cells, HCT-8, produce resistance via an RNA-related mechanism, while prolonged exposures to the fluoropyrimidine is responsible for a DNA-related mechanism of resistance. In addition, cells resistant to short term FUra exposure retain full sensitivity to the continuous exposure to the same agent. These data suggest that biochemical modulation of FUra should take into account the schedule of fluoropyrimidine administration. Based on this rationale, we completed a phase 2 trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients, based upon a hybrid regimen of 2 biweekly-cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) MTX, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with FUra continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect). Among the 33 consecutive patients accrued there were 3 CR and 13 PR (RR = 48%, 95% CL, 31–66%). Eleven patients had a minor response and 4 of them showed tumor shrinkage ranging between 46% and 49%. After a median follow-up time of 26 months, 10 patients are still alive. The median PFS and overall S were 9.6 and 20.2 months, respectively. The low toxicity of the bolus part of our regimen prompted us to pursue its intensification by adding a further modulator to MTX. Our recent finding of a strong synergism between bolus FUra and IFN, obtained in vitro on the same tumor model, generated a phase 2 trial employing the same regimen plus IFN (3,000,000 U im q12 h × 4, starting at the time of FUra bolus administration). Among 42 patients 4 CR, 15 PR (RR = 45%), 6 MR and 10 SD were obtained. Since the results of the two trials are similar showing twice as much activity and less toxicity than bolus FUra + LV or MTX → FUra, a randomized comparison is now ongoing between our original hybrid regimen without IFN and MTX → FUra.

Recently, we have demonstrated that thymidylate synthase (TS) protein expression predicts for the clinical response to a regimen of infusional 5-fluorouracil (5FU) in advanced colorectal cancer patients. Previous studies by other groups that showed a correlation between TS gene expression and response to the fluoropyrimidine also involved infusional regimens. Considering the putatively different mechanism of action of bolus compared with continuous infusion of 5FU, the aim of the present study was to test whether the correlation between TS expression and the clinical response to 5FU is valid for bolus regimens. A secondary aim was to compare TS levels between liver metastases and abdominal recurrences from colon cancer, because these sites have a distinctly different responsiveness to 5FU chemotherapy. The study population consisted of 41 patients (25 males and 16 females; median age, 60 years) with unresectable metastatic or recurrent colon cancer, homogeneously treated with 5FU (420 mg/m 2 i.v., days 1–5) and leucovorin (20 mg/m 2 i.v., days 1–5); cycles were repeated every 28 days. Twenty-seven patients (66%) showed high levels of TS expression as defined by TS scores equal to 3 and 4. The proportion of cases with high levels of TS expression was significantly higher in abdominal recurrences (18 of 22, 82%) compared with liver metastases (9 of 19, 47%; P = 0.02). Intratumoral TS protein expression was inversely correlated with response to chemotherapy (response rate: 7 of 14, 50%, versus 0 of 27 in patients with low and high levels of TS expression, respectively; P = 0.0001). These results confirm that the level of TS protein expression predicts for response to 5FU, even with a bolus schedule. The higher TS levels observed in abdominal compared with liver metastases may account for their different responsiveness to 5FU chemotherapy. Immunohistochemical quantitation of TS protein levels may thus allow us to change the therapeutic approach to advanced colorectal cancer from a general to an individual treatment strategy at a time when new non TS-targeted drugs have become available for this disease.