Background The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. Methods This study analyzed data from ISG‐STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology‐tailored (HT) chemotherapy in adult patients with STS. The 10‐year predicted overall survival (pr‐OS) was estimated with the Sarculator and was stratified into higher (10‐year pr‐OS < 60%) and lower risk subgroups (10‐year pr‐OS ≥ 60%). Results The median pr‐OS was 0.63 (interquartile range [IQR], 0.51‐0.72) for the entire study population, 0.62 (IQR, 0.51‐0.70) for the AI arm, and 0.64 (IQR, 0.51‐0.73) for the HT arm. Three‐ and 5‐year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82‐0.93) and 0.81 (95% CI, 0.71‐0.86) in lower risk patients and 0.69 (95% CI, 0.70‐0.85) and 0.59 (95% CI, 0.51‐0.72) in the higher risk patients (log‐rank test, P = .004). In higher risk patients, the 3‐ and 5‐year Sarculator‐predicted and study‐observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3‐ and 5‐year Sarculator‐predicted and study‐observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105). Conclusions High‐risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS. Lay Summary People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.
Introduction: In head and neck cancer (HNC) patients, fatigue is present throughout the course of treatment and during follow-up. There are limited data about the prevalence and factors associated with fatigue in HNC survivors. The objectives of this study were to assess the prevalence of fatigue and its interference with daily life activities and examine the association between fatigue and gender, age, primary tumour site, Human Papillomavirus (HPV) status, previous oncologic therapy, and time since end of treatment. Methods: Consecutive locally advanced HNC patients having completed curative treatment at least 1 year earlier and free of disease were asked to fill in the Brief Fatigue Inventory (BFI) questionnaire. Fatigue was categorized according to BFI average score as absent (0), mild (>0 to <4), moderate (≥4 to ≤6), and severe (>6 to ≤10). Results: From February 2015 to July 2016, 129 patients (median age = 60 years old; 67% male) were evaluated. Primary sites of cancer were oropharynx (46%, with 4/5 patients HPV positive), nasopharynx (22%), larynx/hypopharynx (14%), oral cavity (13%), and paranasal sinus or salivary gland (5%). Oncologic treatment was completed 12 to 96 months earlier (median = 34 months). Fatigue was reported as absent in 15% of the patients, mild in 67%, moderate in 11%, and severe in 7%. No association between BFI average score and the analyzed variables was identified. Discussion: Moderate and severe fatigue was reported in 18% of HNC survivors. Further research is needed to assess its causes and improve the management.
Objective Outcomes of locally advanced epithelial sinonasal cancers remain unsatisfactory; moreover, only limited and heterogeneous data exist on prognostic factors. Methods We reviewed all consecutive patients with American Joint Committee Cancer stage III to IV epithelial sinonasal cancers treated with platinum‐based induction chemotherapy (IC) followed by locoregional treatment between 1996 and 2015. Results We identified 69 patients treated with a multimodal approach (IC, surgery, radiotherapy). Overall, 44 patients recurred (64%). Of those, 19 patients received salvage surgery, but only four remained disease‐free. Median overall survival (OS) was 62.5 months. Sinonasal neuroendocrine and small cell histotypes (P = 0.0085), neuroendocrine differentiation (P = 0.006), and lack of response to IC (P = 0.03) were associated with worse OS. In patients who recurred, median OS was 13 months since recurrence. Survival was longer in patients submitted to salvage surgery (44%) than in those receiving chemotherapy alone at recurrence (29.5 vs. 4.6 months). Patients with a clinical benefit after palliative chemotherapy had a longer median OS than those with disease progression (29.2 vs. 4.4 months; P < 0.0001). Conclusion Globally, the prognosis of locally advanced epithelial sinonasal cancers is dismal, with worse outcomes for neuroendocrine lesions. In the recurrent setting, feasibility of salvage surgery and clinical benefit from palliative chemotherapy are associated with longer OS. A multimodal treatment strategy with IC seems to offer improved OS when compared with other retrospective series not employing such a therapeutic tool. Level of Evidence 4 Laryngoscope, 130:857–865, 2020
Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood–brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.
Single-nucleotide polymorphisms (SNPs) related to hereditary thrombophilia were investigated as risk factors for thromboembolism in cancer patients. Their effect in metastatic colorectal cancer (mCRC) has never been explored so far. Our aim was to analyse the effect of coagulation factor V (FVL G1691A), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and plasminogen activator inhibitor type 1 (PAI-1 5G/4G) allelic variants in this setting. Fifty-two patients treated with first-line chemotherapy plus bevacizumab who developed a thromboembolic event in their lifetime were initially genotyped. A contemporary cohort of 127 patients who did not experience any thromboembolic event was also analysed. DNA was extracted from peripheral blood and genotypes were determined by real-time PCR, using LightSNiP (TIB MOLBIOL) on LightCcler 480 (Roche). The association between thromboembolism and SNPs was investigated by univariable and multivariable analyses. All SNPs were in Hardy-Weinberg equilibrium (χ test P>0.20). FVL G1691A and PT G20210A were present only in heterozygosis in 4 (2.2%) and 7 (3.9%) patients, respectively; MTHFR C677T in homozygosis in 29 (16.2%), MTHFR A1298C in homozygosis in 13 (7.3%); PAI-1 5G/4G in 98 (54.7%) and 4G/4G in 41 (23%) patients. At univariable analysis, treatment duration was significantly associated with thromboembolism (P<0.001), whereas gender, age, obesity, platelets count and chemotherapy backbone were not. Similarly, FVL G1691A and PT G20210A as well as MTHFR C677T and PAI-1 4G allele were significantly associated, whereas MTHFR A1298C was not. At multivariable model including PT G20210A, MTHFR C677T and PAI-1 4G (age, obesity, treatment duration and chemotherapy backbone were included as adjustment factors), the three SNPs were significantlty associated with higher risk of thromboembolism (P=0.025, <0.0001 and P=0.033, respectively). Further validation studies are warranted in order to design a prospective trial of thromboprophylaxis in mCRC patients with high-risk genotypes.
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