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Determining outcomes using the total neoadjuvant therapy (TNT) in patients with local advanced rectal cancer is important for stratifying patients according to expected outcomes in future studies in the era of treatment combination. The present meta-analysis estimated the pathological complete response, disease-free survival, and overall survival probabilities of rectal cancer patients and identified predictors of outcomes.Studies reporting pathological complete response rate and time-dependent outcomes (progression or death) after total neoadjuvant treatment of locally advanced rectal cancer (LARC) were identified in MEDLINE through January 2022. Three independent observers extracted data on patient populations and outcomes and combined the data using a distribution-free summary survival curve. The primary outcomes were actuarial probabilities of recurrence and survival.Fourteen RCTs, including 18 TNT arms, met the inclusion criteria. The pooled estimate of pathological complete response (pCR) probability was 23.6%, with moderate heterogeneity between studies. The pooled estimates of actuarial disease-free survival rate were 70.6% at 3 years and 65.4% at 5 years. The pooled estimates of actuarial survival rates were 93% at 3 years and 81.6% at 5 years. In both these outcomes, heterogeneity between studies was highly significant.This meta-analysis showed that Total Neoadjuvant Therapy is an optimal approach for LARC patients. The results provide a useful benchmark for future comparisons of the benefits of combinations of other drug families as target therapies or immunotherapies.

We analyzed a cohort of patients with cancer and Sars-Cov-2 infection from the Veneto Oncology Network registry across two pandemic time periods.761 patients with cancer and SARS-CoV-2 infection were included.198 patients were diagnosed during the first pandemic time period (TP1; February 2020 September 2020), 494 during TP2 before the vaccination campaign (TP2/pre-vaccination; September 2020-21 February 2021) and 69 in TP2/post-vaccination (22 February 2021-15 May 2021). TP2 vs TP1 patients were younger (p = 0.004), showed more frequently a good performance status (p0.001) and2 comorbidities (p = 0.002), were more likely to be on active anticancer therapy (p = 0.006). Significantly fewer patients in TP2 (3-4%) vs TP1 (22%) had an in-hospital potential source of infection (p0.001). TP2 patients were more frequently asymptomatic (p = 0.003). Significantly fewer patients from TP2 were hospitalized (p0.001) or admitted to intensive care unit (p = 0.006). All-cause mortality decreased from 30.3% in TP1, to 8.9% and 8.7% in the two TP2 periods (p0.001), reflected by a significant reduction in Sars-Cov-2-related mortality (15.2%, 7.5% and 5.8% in the three consecutive time periods, p = 0.004).Differences in clinical characteristics and features of Sars-Cov-2 infection between TP1 and TP2 reflect the effects of protective measures and increased testing capacity. The lower mortality in TP2 is in line with a less frail population. However, the vast majority of death events in TP2 were related to COVID-19, reinforcing the priority to protect cancer patients.

The psychological impact of the Covid 19 pandemic on cancer patients, a population at higher risk of fatal consequences if infected, has been only rarely evaluated. This study was conducted at the Departments of Oncology of four hospitals located in the Verona area in Italy to investigate the psychological consequences of the pandemic on cancer patients under active anticancer treatments. A 13-item ad hoc questionnaire to evaluate the psychological status of patients before and during the pandemic was administered to 474 consecutive subjects in the time frame between April 27th and June 7th 2020. Among the 13 questions, 7 were considered appropriate to elaborate an Emotional Vulnerability Index (EVI) that allows to separate the population in two groups (low versus high emotional vulnerability) according to observed median values. During the emergency period, the feeling of high vulnerability was found in 246 patients (53%) and was significantly associated with the following clinical variables: female gender, being under chemotherapy treatment, age ≤ 65 years. Compared to the pre-pandemic phase, the feeling of vulnerability was increased in 41 patients (9%), remained stably high in 196 (42%) and, surprisingly, was reduced in 10 patients (2%). Overall, in a population characterized by an high level of emotional vulnerability the pandemic had a marginal impact and only a small proportion of patients reported an increase of their emotional vulnerability.

Aims and objectives To assess the effectiveness of a specific home care nursing programme in addition to standard care in patients (pts) receiving oral anticancer treatments. Background Oral anticancer therapy present challenges for pts since treatment is a home-based therapy. This study evaluates the potentiality of a home care nursing programme in decreasing hospital accesses for not severe toxicity. Methods This is an open-label, multicentre, randomised trial including pts who were receiving an anticancer oral drug. The study complies with the CONSORT checklist published in 2010. Concomitant use of radiation therapy, intravenous or metronomic therapies, or the intake of previous oral drugs was not allowed. Pts were randomly assigned to home care nursing programme (A) or standard care (B). In arm A, dedicated nurses provided information to pts, a daily record on which pts would take note of drugs and dosages and a telephone monitoring during the first two cycles of therapy. The primary outcome was the reduction in improper hospital accesses for grade 1-2 toxicity according to CTCAE v4.0. Results Out of 432 randomised pts, 378 were analysed (184 pts in arm A and 194 in arm B). Hospital accesses were observed in 41 pts in arm A and in 42 pts in arm B (22.3% vs. 21.6%, respectively). No difference was detected in proportion of improper accesses between arm A and arm B (29.3% vs. 23.8%, respectively). Conclusions Our experience failed to support the role of a specific home care nursing programme for pts taking oral chemotherapy. An improved attention to specific educational practice and information offered to pts can explain these results. Relevance to clinical practice Our results underline the role of nurse educational practice and information offered to patients. A careful nurse information of patients about drugs is essential to reduce toxicities avoiding the opportunity of a specific home monitoring.

6511 Background: Since the beginning of the COVID-19 outbreak, the Veneto Oncology Network ROV licensed dedicated guidelines for cancer patients care during the pandemic, and developed a regional registry (ROVID) aimed at describing epidemiology and clinical course of SARS-CoV-2 infection in cancer patients. Preliminary data on 170 patients mainly diagnosed during the first pandemic wave have been published (Guarneri V, Eur J Cancer 2021). Here we report the data of additional 270 patients, comparing clinical data and outcomes between first (W1) and second (W2) pandemic waves. Methods: All patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on diagnosis, comorbidities, anticancer treatments, details on SARS-CoV-infection including source of contagion, clinical presentation, hospitalization, treatments and fate of the infection are recorded. Results: 440 patients have been enrolled, 196 diagnosed during W1 (until September 2020) and 244 during W2. The most common cancer type was breast cancer (n = 116). Significant differences in clinical characteristics between W1 and W2 were the followings: ECOG PS 0 (34% vs 58%), presence of cardiac comorbidities (30% vs 13%), presence of any co-morbidities (81% vs 62%), smoking habits (23% vs 13%). Patients diagnosed in W1 were less likely on active anticancer therapy (54% vs 73%) at the time of SARS-CoV-2 infection. Distribution per stage, presence of lung metastases, disease setting (curative vs palliative), active treatment discontinuation due to infection were similar between W1 and W2. Patients diagnosed in W1 were more likely symptomatic for SARS-CoV-2 infection (80% vs 67%), and reported more frequently an in-hospital contact as potential source of infection (44% vs 9%). Significantly more patients diagnosed in W1 were hospitalized (76% vs 25%). All-cause mortality rates were 30.6% for patients diagnosed in W1 vs 12% for patients diagnosed in W2 (p < 0.001). However, deaths due to SARS-CoV-2 infection were more frequent in patients diagnosed in W2 (86% vs 54%, odds ratio 3.22; 95% CI 1.97-5.279). Conclusions: Differences in clinical characteristics between W1 and W2 reflect different pattern of virus circulation. The dramatic reduction of in-hospital contact as a source of infection reflects the efforts put in place to protect this vulnerable population from in-hospital exposure. The lower all-cause mortality rate observed in W2 is in line with the observed less frail population. However, the higher relative risk of death due to SARS-CoV-2 infection observed in W2 reinforces the need to adopt protective measures including vaccination in cancer patients, irrespectively of age, stage, and comorbidities.

Summary Background: It has been proposed that the activity of a secondline treatment regimen can be documented by showing that the time to progression (TTP) following second-line therapy is longer than the TTP following first-line therapy in the same patients. Patients and methods: The ratio of TTP during first and second-line therapy, identified as the growth modulation index (GMI), was determined in 34 patients with advanced colorectal cancer. First-line chemotherapy consisted of one of several schedules of leucovorin (LV)-modulated 5-fluorouracil (5-FU) or raltitrexed. Second-line therapy consisted of the combination of LV-modulated 5-FU and oxaliplatin (1-OHP). Patients were switched to second-line therapy upon evidence of progressive disease following first-line therapy. Results: Median TTP following first-line therapy was 13 weeks (95% confidence interval (CI): 7.6-18.7), while median TTP following second-line therapy was 31 weeks (95% CI: 21.3-41.0). Sixteen patients (47%; 95% CI: 35%-59%), showed a GMI ^ 1.33, while the remaining 18 patients (53%; 95% CI: 40%l-66%>) had a GMI < 1.33. Log-rank analysis of the Kaplan-Meier curves of TTP following first- versus secondline therapy demonstrated a statistically significant difference in favour of second-line therapy (P = 0.0081). Conclusions: This study demonstrates the utility of the GMI as a tool for assessing the activity of novel second-line therapeutic programs.

6597Background: Patients (pts) receiving anticancer oral therapy need a specific training since treatment is a home-based therapy. Published data suggest the benefit of an active monitoring by mean...

The high specificity and sensitivity of testicular tumor markers make them particularly useful in the management of these neoplasms. Basal value represents an independent prognostic variable, influencing the choice of therapy. An increase in marker level before chemotherapy could also acquire a powerful prognostic significance. The decay curve pattern is indicative of the radicality of surgery. Also during chemotherapy the behavior of markers conditions further therapeutic strategies.

Two hundred and forty six consecutive patients with pathological T1-2 N0 M0 non-small cell lung cancer were reviewed. Median follow-up was 79 months (range 3-144). So far, 110 patients have relapsed (45.6%). Actuarial median time to recurrence was 26 months in the 45 patients with thoracic relapses versus 12 months of the 65 metastatic (P0.001). Disease-free survival (DFS) rates at 5 and 10-year were 62 and 49%, respectively. Fifteen percent of the patients (20) disease-free at 5 years relapsed in the following years; of them, 40% (8) underwent new surgery. Extrapulmonary malignancies other than lung cancer occurred in 27 patients (11.2%), mostly (21) after the diagnosis of lung cancer; in this subset median time to occurrence was 52 months (range 8-105) with a rate of occurrence remaining constant over the years after operation. Univariate and multivariate analysis demonstrated that large cell histology, lower performance status (PS) and presence of symptoms were unfavourable prognostic factors both for DFS and survival.this study found a non-negligible proportion of late events and identified some prognostic factors (PS, presence of symptoms and large cell histology) using information obtained from routine data.

e13514 Background: Endoxifen (EN), the main active metabolite of tamoxifen (T), reaches steady state (SS) plasma levels after about 4 months of administration. It derives principally by cytochrome CYP2D6 activity, which is highly variable among patients. In order to predict individual SS EN exposure, three different approaches were investigated. Methods: Before starting T administration, 73 breast cancer patients (median age: 59 yrs, range: 30-89) were characterized by means of: 1) a phenotyping test of CYP2D6 activity, based on the urinary metabolic ratio of dextromethorphan/dextrorphan (log transformed, LMR). 2) CYP2D6 genotyping (alleles *1, *3, *4, *5, *6, *9, *10, *41), to classify patients in 3 functional groups: Extensive (EM), Intermediate (IM) and Poor (PM) Metabolizers. After starting T treatment (20mg/day), EN plasma levels were measured after 1 month (1M EN, pre- steady state) and 4 months of therapy (SS EN). ANOVA, paired and unpaired T test and linear regressions were performed to analyze associations between LMR, CYP2D6 genotype, 1M EN and SS EN. Multivariate linear regression was used to create a predictive equation; its mean prediction and absolute errors (MPE% and MAE%) and the positive and negative predictive values (PPV% and NPV%, according to median SS EN) were calculated. Results: SS EN plasma levels varied between 2.4 and 39.2 (median: 8.7) ng/ml. LMR (median: -1.6; range: -3.1- +1.2) showed a significant linear correlation with SS EN (r=-0.59; p

The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low (or = 25% of stained cells) or high (25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3-58). Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive (or = 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analysis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.

9063 Background: Advanced soft tissue sarcomas (STS) relapsing after first line chemotherapy are incurable. There is no standard treatment for patients (pts) relapsing after Doxorubicin and Ifosfam...

Aims and Background To identify the maximum tolerated doses and to define the activity of a regimen incorporating leucovorin (LV)-modulated 5-fluorouracil (5-FU) bolus and continuous infusion, oxaliplatin (I-OHP) and irinotecan (CPT-11) in patients with advanced, 5-FU-refractory colorectal cancer (CRC). Patients and Methods Starting doses: LV 100 mg/m2 as a 2-hour infusion followed by 5-FU 300 mg/m2 bolus administration followed by 5-FU 500 mg/m2 as a 22-hour infusion on days 1 and 2; I-OHP 65 mg/m2 as a 2-hour infusion concomitantly with LV on day 1; CPT-11 90 mg/m2 concomitantly with LV on day 2. Planned cycle interval: 2 weeks. Results Two hundred twenty-six cycles were administered to 27 patients. Recommended doses were 5-FU bolus 300 mg/m2, 5-FU protracted infusion 500 mg/m2, l-OHP 75 mg/m2, and CPT-11 150 mg/m2. Among 25 patients evaluable for response we observed 13 disease stabilizations (52%; 95% CI: 33-71%), 6 instances of disease progression and 6 responses (24%; 95% CI: 7-41%). Median time to progression and overall survival were 24 and 60 weeks, respectively. A cycle delay >3 days was observed in 134/199 cycles (67%). Conclusions This study confirms the feasibility of triplet chemotherapy in patients with advanced 5-FU-refractory CRC.