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Cigarette smoking is the main risk factor for head and neck cancer (HNC) and many HNC patients are active smokers at diagnosis. We conducted a systematic literature review and meta-analysis to quantify the survival impact of smoking cessation at or around the time of HNC diagnosis. We searched studies published until December 31, 2021, and used random-effects meta-analysis to pool study-specific estimates into summary hazard ratio (SHR) and corresponding 95% confidence intervals (CI). Sixteen studies were published between 1983 and 2021, and over 2300 HNC patients were included. Studies were diverse in terms of design, patients, tumours and treatment characteristics, and criteria used to discriminate quitters from continued smokers. HNC patients who quit smoking at or around diagnosis had significantly better overall survival than continued smokers (SHR 0.80, 95% CI 0.70-0.91, n studies = 10). A beneficial effect of post-diagnosis smoking cessation was suggested for other survival endpoints as well, but the results were based on fewer studies (n = 5) and affected by publication bias. Cessation counselling should be offered to all smokers who start a diagnostic workup for HNC and should be considered standard multidisciplinary oncological care for HNC patients. PROSPERO registration number CRD42021245560.

BackgroundWomen and men differ genetically, biologically (sex) and by social construct (gender), possibly impacting on prognostic factors in predicting cancer survival. Hemoglobin levels and immune system activation are players acting in this scenario which could play a role in partly determining prognosis between patients of different sex/gender (S/G). Here, we investigate these factors in patients affected by tongue squamous cell carcinoma.MethodsThis is an observational retrospective cohort study. We collected tongue cancer patients’ clinical data, including hemoglobin levels and neutrophil lymphocyte ratio (NLR). Overall survival (OS) and disease-free survival (DFS) were compared between women and men considering confounding and prognostic factors in multivariate Cox proportional hazard models. Stratified analyses were also conducted by sex and tumor stage.Result576 patients, 39.9% women and 60.1% men, were found eligible for the analysis. Men were more often smokers (p2.37, who did not performed Radiotherapy and with depth of invasion (DOI)> 10 were associated with a significant increase in relapse and death (all pConclusionIn our cohort of patients with oral tongue squamous cell carcinoma, men present better OS and DFS than women with early stages tumors. Low hemoglobin level was an independent prognostic factor for women, especially at early-stage tumors. For advanced stages (III-IV), sex is not a significant factor related to patients’ prognosis.

We reviewed the studies examining whether quitting smoking at or around diagnosis favourably affects the prognosis of bladder cancer (BC) patients, who are often active smokers at diagnosis. We found only nine eligible articles published until 31 January 2022, which encompassed around 5500 BC in total, the majority of which were nonmuscle invasive BC (only one paper included muscle-invasive BC). We used random effects meta-analysis to obtain a summary hazard ratio (SHR) and 95% confidence intervals (CI). The median proportion of smokers who quit at or around diagnosis was 29.8% (range 8.4–43.1%). For the overall, BC-specific, and progression-free survival, the studies were limited in number (n = 3) and provided conflicting results. At the same time, quitters did not appear to have a lower risk of recurrence than continued smokers (SHR 0.99, 95% CI 0.61–1.61). In conclusion, while the evidence is currently not sufficient to draw firm conclusions (especially for patients with muscle-invasive BC), physicians should not refrain from educating smoking BC patients about the benefits of smoking cessation and provide the necessary support.

Metaplastic breast cancer (MBC) and triple-negative (TN) BC of no special type are often confounded with each other in terms of survival and prognosis. In this systematic study and meta-analysis, we evaluated the prognosis of each of these two different diagnoses.We conducted a systematic literature search and review using the MOOSE guidelines, through PUBMED database, the Ovid MEDLINE database, and the ISI Web of Science Citation Index Expanded (SCI Expanded). Overall survival (OS) and disease-free survival (DFS) were the main outcomes considered.Our review eventually selected six independent studies, with a total of more than 59 519 patients. MBC was found to associate with worse OS compared to TNBC of no special type, with a significant 40% increased risk of death [summary hazard ratio (SHR) = 1.40, 95% confidence interval (CI): 1.30-1.50]. We found neither heterogeneity ( I2 = 0%) nor evidence of publication bias ( P = 0.82 and P = 0.49 by Begg's and Egger's test, respectively) between studies. No statistically significant difference was found between MBC and TNBC of no special type in terms of DFS (SHR = 1.17, 95% CI: 0.80-1.71).This study demonstrates that TNBC of no special type and MBC have comparable DFS, although the latter presents a significantly worse prognosis in terms of OS. Despite DFS being similar in both subtypes, this did not result in significant OS benefits, with MBC score being the worse of the two diseases.

The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/− chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (p = 0.03) and the activation of nutritional counselling (p = 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting.

Purpose Initial findings in patients with cancer suggest a lower seroconversion to SARS-COV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunization (AEFI) to the BNT162b2 vaccine in patients on active treatment. Patients and methods Cancer patients candidate to two doses of BNT162b2 SARS-COV-2 vaccination were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG

3063 Background: Several studies showed that high baseline tumor size (BTS) is associated with worse outcomes in cancer patients treated with immunotherapy (IO). However, the prognostic impact of BTS for patients receiving targeted therapies (TT) remains uncertain. Methods: We collected clinical data for patients with solid tumors consecutively treated within early phase trials at our institution from 01/2014 to 04/2021. Treatments were categorized as IO-based (if any IO-agent was included) or TT-based (biomarker-matched or not). BTS was calculated as the sum of RECIST 1.1 baseline target lesions. Progression-free survival (PFS), overall survival (OS) and objective-response rate (ORR) were compared between patients with high BTS (> median) and low BTS (≤median). Results: 444 patients were eligible for the analysis (220 IO, 151 TT biomarker-matched, 73 TT biomarker-unmatched). Median age was 56 years (interquartile range, IQR 48-64) and median BTS was 69 mm (IQR 40-100). Most represented tumor types were breast (49%), lung (9%), melanoma (5%) stomach, colorectal, head and neck and ovarian (4% each). Patients with low BTS were more often female (p < 0.001), had a better performance status (PS, p = 0.008), lower LDH (p < 0.001), lower neutrophile/lymphocyte ratio (NLR, p < 0.001) and higher albumin (p = 0.003). OS was significantly longer for patients with low BTS (16.6 vs 8.2 months, p < 0.001), including when restricting at those receiving IO (12 vs 7.5 months, p = 0.005). Among patients receiving TT, those with lower BTS experienced longer PFS (4.7 vs 3.1 months, p = 0.002) and OS (20.5 vs 9.9 months, p < 0.001) as compared with those with high BTS. However, BTS was only prognostic among patients receiving biomarker-matched TT, with improved PFS (6.2 vs 3.3 months, p < 0.001) and OS (21.2 vs 6.7 months, p < 0.001) in the low-BTS subgroup, despite a similar ORR (28% vs 22%, p = 0.57). BTS was instead not prognostic among patients receiving unmatched TT, with similar PFS (3.7 vs 4.4 months, p = 0.30), OS (19.3 vs 11.8 months, p = 0.20) and ORR (33% vs 28%, p = 0.78) in the two BTS groups. Multivariate analysis confirmed that BTS was independently associated with PFS (p = 0.03) and OS (p < 0.001) but not with ORR (p = 0.11), regardless of tumor site, treatment category, PS, NLR, sites of metastases and number of prior lines. Conclusions: Patients receiving biomarker-matched TT experience longer PFS and OS if having a lower BTS, whereas response rate is not affected by this variable. This difference may reflect the faster emergence of molecular mechanisms of resistance among patients with higher baseline burden. Lower BTS is also confirmed to be associated with longer survival among patients receiving experimental IO. BTS has instead no prognostic value among patients receiving unmatched TT.

9541 Background: Immune-checkpoint inhibitors (ICI) and targeted-therapies (TT) have become standard options for BRAF -V600 metastatic melanoma (B-mut MM) patients. However, still more than 50% of those patients do not respond or relapse to these current strategies. Preclinical and translational data suggest that ICI plus TT may improve treatment outcomes in patients with B-mut MM, but with conflicting results in the clinical setting. Methods: We performed a systematic review and meta-analysis of randomized phase II-III studies published until January 2022 comparing first-line ICI+TT vs TT alone in B-mut MM. We obtained summary estimates through random-effects models. Overall survival (OS) and progression-free survival (PFS) were the main outcomes retrieved but we look also at difference in responses and adverse events. Results: We summarized data from 3 independent trials and we showed a significant advantage in terms of PFS and OS for the experimental arms in B-mut MM patients treated with ICI+TT rather than TT alone. The summary estimate indicates a significant 23% decrease in risk of progression (SHR = 0.77, 95%CI: 0.66-0.89, with no between-study heterogeneity I2= 0%) and a significant 21% reduction in risk of death (SHR = 0.79, 95%CI: 0.66-0.96, with no heterogeneity I2= 0%). However, no difference was shown (p-value = 0.56) between arms in terms of summary Objective Response Rate (ORR) estimates (Summary ORR doublet = 65.4% [61.5%; 69.2%] and Summary ORR triplet = 67% [63%; 70.9%], respectively). From the subgroup analysis on PFS risk estimates, no significant differences were observed in summary HRs by age ( < 65 vs ≥65 years, p-value = 0.11), sex (female vs male, p-value = 0.58), ECOG PS (0 vs 1, p-value = 0.36), LDH levels (lower vs upper, p-value = 0.59) and PDL1 status (positive vs negative, p-value = 0.89). Significant differences were found in frequencies of grade 3 or more adverse events with higher number of events occurring in B-mut MM vs TT alone (Summary Odd Ratio = 2.01, 95%CI: 1.16-3.47, I2= 74%), whereas no significant differences were found in terms of any adverse event between arms (SOR = 1.83, 95%CI: 0.70-4.78, I2= 0%). Conclusions: This study supports and extend the discussion on first-line available combinations to be offered to B-mut MM patients. Combining ICI with TT demonstrated an effective advantage on both PFS and OS, although augmenting toxicities. Further biomarker-driven investigation may identify patient subpopulations who could benefit from ICI+TT combinations in order to expand their window of therapeutic opportunities.