Madam — Italy has been experiencing one of the world's deadliest COVID-19 outbreaks, and all healthcare facilities, including radiotherapy departments, have faced the unprecedented emergency. In order to investigate how radiotherapy directors in Lombardy (northern Italy) have managed the crisis, an online questionnaire (27 questions) via Google Forms, based on the first published COVID-19 reports, was sent to 34 CODRAL (Board of Directors of Radiation Oncology Departments in Lombardy) directors. Thirty-one (91%) specialists anonymously completed the survey. Within a few days of the outbreak, more than 75% of hospitals became COVID-19 centres. Following institutional indications, more than 80% of directors decided to interrupt or modify radiotherapy for some pathologies, preferring short treatments and home assistance where possible. About a half of centres reduced their clinical activity by 10–50%. Most hospitals (84%) cancelled out-patient follow-up visits and some (68%) activated telematic consultations. Triage procedures were adopted in virtually all centres. Almost a half of centres registered COVID-19-positive or suspected patients, and for some of them treatment was suspended. Nearly all radiotherapy centres declared that they would provide healthcare staff with surgical masks and gloves, while only a few of them also made other personal protective equipment available, including class II and III filtering facepieces (FFP2 and FFP3). Working from home solutions were adopted in about 30% of facilities. More than a half of centres had personnel in quarantine (between one and 12 persons off service). A considerable proportion of hospitals activated psychological support for patients and/or personnel. Our report shows how Lombardy radiotherapy departments have rapidly coped with the COVID-19 disruption. Significant reorganisation has been carried out in a short time with conversion to COVID-19 activities (wards, physicians transfer) and changes in radiotherapy practice. The priority was a balance between cancer patient care and safety, while protecting the healthcare professionals and providing any possible support in COVID-19 activities. The authors declare no conflict of interest.

TPS196 Background: Concomitant chemoradiation (CRT) is the standard treatment for locally advanced squamous cell carcinoma (LASCC). RT plus cetuximab is superior to RT alone and it is an alternative treatment to CRT (Bonner, NEJM 2006). The efficacy of induction chemotherapy when added to standard treatment has never been demonstrated, however, induction cisplatin/fluorouracil [PF] plus docetaxel combination (TPF) is superior to PF when added to CRT or RT alone (Posner, NEJM 2005; Vermorken, NEJM 2005). Methods: This ongoing factorial phase III study is the implementation of a previous phase II randomized trial evaluating the efficacy of CRT with or without induction TPF. At the end of the phase II study a Monitoring Committee decided to continue the study as a phase III, as initially planned, based on the efficacy and safety data of the phase II study. This phase III four arm factorial study has now randomized 352 patients (target 420) with LASCC unresectable stage III-IVM0 of oral cavity, oropharynx, hypopharynx, age > 18 years, ECOG PS 0-1, measurable disease by RECIST, adequate organ function. One step randomization is adopted to assign patients to concomitant treatment alone CRT (arm A1) or RT/cetuximab (arm A2) or to 3 cycles of induction TPF followed by CRT (arm B1) or RT/cetuximab (arm B2). Two concomitant PF cycles are administered in the CRT arm. Primary endpoints are the comparison of 3-year overall survival (OS) between induction vs no induction and the incidence of G3-4 in-field toxicity between CRT and RT/cetuximab. During the planned ad-interim analysis, the Independent Data and Safety Monitoring Committee decided to increase the sample size from the initially planned 350 patients to 420 to detect an absolute difference of 12% in 3 years OS in favour of the induction arm. Assuming an hazard ratio of 0.675 this study will have 80% statistical power with a two-sided type I error of 0.05. The total number of 420 patients will also be able to detect a difference of 10%, in grade 3-4 in-field toxicity between CRT vs RT/cetuximab with a power of 80%.

6000 Background: Concomitant CT/RT is the standard treatment for locally advanced head and neck squamous cell carcinoma. This trial explores the efficacy of induction chemotherapy with TPF before concomitant CT/RT and concomitant CT/RT alone in locally advanced unresectable disease. Patients and Methods: From January 2003 to January 2006, 101 patients (pts) with stage III- IV M0, PS 0–1, were randomized to 2 cycles of cisplatin (P) 20mg/sqm days 1–4, 5FU (F) 800 mg/sqm 96-hour CI wks 1 and 6 during RT (66–70 Gy) (Arm A) or 3 cycles TPF (docetaxel 75 mg/sqm and P 80 mg/sqm on day 1, F 800 mg/sqm 96 hours CI) every 3 weeks followed by the same CT/RT (Arm B). Neck dissection was planned for pts with stage N2-N3 and pathological complete response (CR) at the primary tumor. A minimum accrual of 96 pts was required to detect a difference in radiological CR (primary endpoint) of at least 15% in favor of arm B. Results: Pts/tumor characteristics were well balanced in the two arms. During TPF, G3–4 neutropenia was the main hematological toxicity (52%) while nonhematological toxicities were mild. CR rate after TPF was 6.5%. During concomitant CT/RT, hematological and nonhematological toxicities were not increased in the experimental arm B and the feasibility of CT/RT was not compromised. Grade 3–4 toxicities in arms A and B, respectively, were mucositis 38% and 25%, dysphagia 21% and 16%, skin reaction 13% and 15%, weight loss 2% and 4%. Radiological evaluation (CT or MRI scan) of responses 6–8 weeks from the end of CT/RT showed a CR of 21.2% (CI: 64–89) in arm A and 50.0% (CI: 34–65) in arm B. Radiological CRs at 8 months for unresected pts were 40.0% in Arm A and 57.1% in Arm B. Median OS and 1-yr OS were respectively 33.3 months and 77.6% in Arm A, while median OS was not reached in arm B and 1-yr OS was 86.0%. Conclusions: Neoadjuvant TPF is feasible and does not compromise subsequent concomitant CT/RT. Compared with CT/RT, induction TPF plus CT/RT significantly improves clinical CR evaluated at 8 weeks and 8 months after the end of the treatment. A trend for improved OS was also observed. The phase III part of the study with survival as the primary end-point is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

5518 Background: Concomitant CT/RT is the standard treatment for LASCCHN. Induction chemotherapy followed by CT/RT vs CT/RT alone have not yet been compared. The feasibility of TPF followed by CT/RT has been evaluated in a previous study (Int J Rad Oncol Biol Phys 2004, 59:481). Methods: Pts with inoperable stage III-IVa, PS 0–1, were randomized to CT/RT [2 cycles of Cisplatin 20 mg/sqm days 1–4, 5FU 800 mg/sqm 96 hours c.i. weeks 1 and 6 during RT (66–70 Gy)] (Arm A) or 3 cycles of neoadjuvant TPF (Docetaxel 75mg/sqm day1, Cisplatin 80mg/sqm day1, 5FU 800mg/sqm 96 hours c.i) followed by the same CT/RT (Arm B). Pts were stratified according to tumor site, T stage and nodal status. Neck dissection was performed in N2-N3 patients with pathological CR on primary tumor. The planned sample size was 96 pts to detect a difference in CR (primary endpoint) up to 15% in favour of arm B. The radiological responses were evaluated by an internal committee according to RECIST criteria. Results: Preliminary data are available for 84/96 randomized pts (42 arm A, 42 arm B). Pts/tumor characteristics are well balanced in the two arms. Toxicities during induction TPF consisted primarily of G3–4 granulocytopenia 56% (febrile neutropenia: 7.5%). Grade 3–4 toxicities during CT/RT in arm A and B were mucositis (42% and 26%), dysphagia (20% and 9%), skin reaction (12% and 8.6%), asthenia (5% and 3%); G3 weight loss (2% and 3%), G3 dry-mouth (0% and 3%). Duration of CT/RT was equivalent: 6.1 wks (4.2–8.7) in arm A and 6.3 wks (3.8–9.5) in arm B. At the end of CT/RT, in the 82 pts evaluable for efficacy, radiological CR were 20% (95% CI 8–37%) in arm A and 64% (95% CI 45–80%) in arm B. Conclusions: Three cycles of neoadjuvant TPF are feasible and don’t compromise subsequent concomitant CT/RT with comparable toxicity pattern. At the end of the treatment sequence serious adverse events were 31% in arm A and 34% in arm B. The difference in CR of 40% in favour of arm B justifies the following phase III study. Final results including pCR and DFS will be presented at the meeting. [Table: see text]

In the present work, the protective properties of inhibitive pigments in two epoxy‐primers against corrosion of the aluminium alloy 2024T3 in marine atmosphere were investigated, the first containing SrCrO4 and the second Zn3(PO4)2. Potentiostatic polarisation and impedance measurement methods were utilised to evaluate, both the spontaneous onset of defects on coated samples and the propagation of a small artificial defect of known dimension applied since the beginning of the test on each sample, during 24 months of exposure to the marine atmosphere. These techniques enabled a quantitative evaluation of the protective efficiency of the two primers to be made, and for the effects of the surface pre‐treatments of the metallic substrate to be investigated.

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.

Aims and background: To evaluate the rate of cancer patients who do not fill out a quality of life (QL) questionnaire, their characteristics and the reasons for not filling out the QL questionnaire.Methods: Consecutive cancer patients who were seen in 79 Italian medical oncology and radiotherapy centers over a period of one week were asked to fill out a questionnaire concerning the importance of 46 domains of quality of life, each one scored on 4 levels (not at all, a little, much, and very much).Results: Of 6,918 cancer patients, 820 (11.9%) did not fill out the questionnaire. The most important reasons for not complying were: illiteracy (17.9%), lack of glasses or poor eye-sight (17.4%), poor physical condition (11.9%), poor psychological condition (5.9%), refusal (28.7%). The questionnaires significantly less filled out were those of older patients with low performance status and educational level or with locally advanced or disseminated disease and inpatients.Conclusions: The results of the study reveal the risk of selection bias in QL assessment in randomized controlled trials and suggest the need for more complete information regarding the aim of QL evaluation and the necessity of a proxy's help to overcome the problem, with the awareness that the proxy's influence could modify the response. The impact of the lack of patient compliance on the QL results still remains to be evaluated.

Purpose: A prospective observational multicenter trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RTE), and evaluate the use of antiemetic drugs in radiation oncology clinical practice.Methods and Materials: Fifty-one Italian radiation oncology centers took part in this trial. The accrual lasted 2 consecutive weeks, only patients starting radiotherapy in this period were enrolled. Exclusion criteria were age under 18 years, and concomitant chemotherapy. Evaluation was based on diary cards filled in daily by patients during radiotherapy and I week after stopping it. Diary cards recorded the intensity of nausea and any episode of vomiting and retching. Prophylactic and symptomatic antiemetic drug prescriptions were also registered.Results: Nine hundred thirty-four patients entered the trial, and 914 were evaluable. Irradiated sites were: breast in 211 patients, pelvis in 210 patients, head and neck in 136 patients, thorax in 129 patients, brain in 52 patients, upper abdomen in 42 patients, skin and/or extremities in 37 patients, and other sites in 97 patients. Vomiting and nausea occurred in 17.1% and 37.3% of patients, respectively, and 38.7% patients had both vomiting and nausea. At multifactorial analysis, the only patient-related risk factor that was statistically significant was represented by previous experience with cancer chemotherapy. Moreover, two radiotherapy (RT)-related factors were significant risk factors for RIE, the irradiated site and field size. In fact, a statistically significant higher percentage of RIE was registered in upper abdomen RT and RT fields > 400 cm(2). Although nonstatistically significant, patients receiving RT to the thorax and head and neck presented a higher incidence of RIE. Only a minority (14%) of patients receiving RT were given an antiemetic drug, and the prescriptions were more often symptomatic than prophylactic (9% vs. 5%, respectively). Different compounds and a wide range of doses and schedules were used; however, there is some evidence from our data that in spite of antiemetic prophylaxis, 46% of patients had vomiting, and 58% had nausea. The majority (93%) of the prophylactic group received oral 5-hydroxytriptamine receptor (5-HT3) antagonist (8 mg/day, 7 days/week). In the symptomatic group, 54% and 41% patients received 5-HT3 antagonists and metoclopramide, respectively. At multivariate analysis, no patient- or PT-related risk factor for RIE was found to influence significantly the prophylactic or symptomatic use of antiemetics.Conclusion: Our study provided useful data on epidemiology and characteristics of RIE. Previous chemotherapy, field size, and irradiated site (upper abdomen) were the only significant prognostic factors of RIE. A remarkable incidence of RIE was found in patients submitted to thoracic and head and neck RT. With this background of knowledge, it will be possible to better plan further studies on this important problem. Moreover, the low rate of antiemetics use and the wide variety of doses and schedules employed suggest the need to reinforce the "evidence based" approach to identify the best antiemetic approach to RIE. (C) 1999 Elsevier Science Inc.

Background: Studies are available showing that cancer patients in southern Europe may be less well informed about their disease than patients in northern Europe and North America.Patients and methods: In the framework of a survey aimed at exploring the meaning of quality of life for the Italian cancer patient, carried out all over Italy in a one-week time span on 6098 consecutive patients, two visual analogue scales evaluating severity and curability of disease were also submitted to the patients. Four patterns of patients' answers were defined: very easy/difficult-to-cure disease, and not-severe/severe disease. Multifactorial analyses were performed using logistic models for each of the four responses, assuming patient characteristics, time since diagnosis and disease extent as explanatory variables.Results: Only 26% of 2088 patients with disseminated disease believed it to be 'difficult to cure', while 39% felt it to be 'easy to cure'. In the same subgroup of patients, only 47% found their disease `severe'.Conclusions: Authors were impressed by these unexpected results, which are therefore reported separately from the overall analysis of data, aimed at exploring the quality of life domains for the Italian cancer patient. In fact, they would suggest a great lack of awareness of the severity and curability of their disease in a large group of unselected Italian cancer patients. This may depend on various factors, including cross-cultural ones, but could also be partly related to inadequacies in the process by which the Italian patient is informed, and this should be further investigated.

Aims and background The role of radiotherapy in the treatment of stage III non-small cell lung cancer is controversial. The aim of this survey was to investigate the use of this modality in current clinical practice in Lombardy, a highly industrialized region of northern Italy. Methods A questionnaire was sent to all 13 radiotherapy centers in Lombardy, covering statistical, clinical, technical and strategical aspects, and the responses were analyzed. Results A wide range of attitudes was observed among participating radiation oncologists; the percentage of cases treated with curative intent varied largely between centers (4-100%), as did the proportion of patients given to radiation only rather than combined modality treatment (5-100% vs 0-90%). Conclusions An urgent need exists for better cooperation between all clinicians involved in lung cancer treatment, pursuing the goals of a more uniform clinical practice and a more aggressive clinical research attitude.

From January 1981 through December 1983, 49 untreated patients with locally advanced head and neck cancers were randomized in two groups to receive different radiochemotherapy regimens. Group A, including 29 cases, received 4 cycles of induction chemotherapy with Bleomycin, Methotrexate and Hydroxyurea before definitive external radiotherapy (60 Gy); group B, including 20 patients, received the same total dose of radiotherapy but the 4 cycles of chemotherapy, as described above, were administered between the 20- and the 40-Gy doses. Both groups were compared with a control group treated in the same period with radiotherapy (60 Gy) alone. The response to treatment was evaluated at the end of chemotherapy or radiotherapy alone and at the end of combined regimens. Long-term survival rates were analyzed for all groups relative to complete tumor response, disease-free interval and time to disease progression. In our experience the radio-chemotherapy combination, according to the described schedules, failed to improve both local control and overall survival; the comparison with the control group does not suggest that induction or intercalated chemotherapy can increase long-term survival even if initial complete and partial response rates are high.

6 patients with severe chronic progressive multiple sclerosis were subjected to total lymphoid irradiation (TLI) to assess clinical efficacy and side effects. During a 4 year follow-up the disability progression was continuous. Side effects during TLI were well tolerated; side effects after TLI brought about a worsening of the quality of life. One patient died of pneumonia. In this preliminary study TLI did not reduce the worsening of disability in MS patients.