Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview

Colorectal carcinoma is the second leading cause of cancer-related deaths, and indeed, rectal cancer accounting for approximately one third of newly diagnosed patients. Gold standard in the treatment of rectal cancer is a multimodality approach, aiming at a good control of the local disease. Distant recurrences are the major cause of mortality. Currently, Locally Advanced Rectal Cancer (LARC) patients undergo a combined treatment of chemotherapy and radiotherapy, followed by surgery. Eventually, more chemotherapy, namely adjuvant chemotherapy (aCT), may be necessary. Total Neoadjuvant Therapy (TNT) is an emerging approach aimed to reduce distant metastases and improve local control. Several ongoing studies are analyzing whether this new approach could improve oncological outcomes. Published results were encouraging, but the heterogeneity of protocols in use, makes the comparison and interpretation of data rather complex. One of the major concerns regarding TNT administration is related to its effect on larger and more advanced cancers that might not undergo similar down-staging as smaller, early-stage tumors. This minireview, based on a systematic literature search of randomized clinical trials and meta-analysis, summarizes current knowledge on TNT. The aim was to confirm or refute whether or not current practice of TNT is based on relevant evidence, to establish the quality of that evidence, and to address any uncertainty or variation in practice that may be occurring. A tentative grouping of general study characteristics, clinical features and treatments characteristics has been undertaken to evaluate if the reported studies are sufficiently homogeneous in terms of subjects involved, interventions, and outcomes to provide a meaningful idea of which patients are more likely to gain from this treatment

Untailored vs. Gender- and Body-Mass-Index-Tailored Skeletal Muscle Mass Index (SMI) to Assess Sarcopenia in Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

: (1) background: sarcopenia lasting >1 year might be considered a chronic condition in many HNSCC patients. CT-scan-derived skeletal muscle mass Index (SMI) is an established surrogate of sarcopenia; yet, the cut-off reported in the literature (literature-based, lb-SMI < 43.2) is mainly based on the risk of chemoradiotherapy-induced toxicity, and the optimal value to discriminate OS is under-investigated. (2) methods: the effect on OS of the lb-SMI cutoff was compared with an untailored OS-oriented SMI cutoff obtained in a cohort of consecutive advanced HNSCC patients treated with primary chemoradiotherapy, bio-chemotherapy or chemo-immunotherapy (cohort-specific, cs-SMI cutoff). gender- and BMI-tailored (gt-SMI and bt-SMI) cut-offs were also evaluated. cutoff values were identified by using the maximally selected rank statistics for OS. (3) results: In 115 HNSCC patients, the cs-SMI cutoff was 31.50, which was lower compared to the lb-SMI reported cut-off. the optimal cut-off separately determined in females, males, overweight and non-overweight patients were 46.02, 34.37, 27.32 and 34.73, respectively. gt-SMI categorization had the highest effect on survival (p < 0.0001); its prognostic value was independent of the treatment setting or the primary location and was retained in a multivariate cox-regression analysis for OS including other HNSCC-specific prognostic factors (p = 0.0004). (4) conclusions: a tailored SMI assessment would improve clinical management of sarcopenia in chemoradiotherapy-, bio-chemotherapy- or chemo-immunotherapy-treated HNSCC patients. gender-based SMI could be used for prognostication in HNSCC patients

Factors predicting pathological response to neoadjuvant chemoradiotherapy in rectal cancer: the experience of a single institution with 269 patients (STONE-01)

Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27-0.93 and p = 0.003; OR: 0.42, CI: 0.24-0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time

The Italian Association of Radiotherapy and Oncology Recommendation for Breast Tumor Recurrence: Grades of Recommendation, Assessment, Development and Evaluation Criteria

: Salvage mastectomy is currently considered the standard of care for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and postoperative radiotherapy (RT). Alternative treatment options for these patients, such as a second BCS followed by repeated RT, have been suggested. The panel of the Italian Association of Radiotherapy and Clinical Oncology developed clinical recommendations for second BCS followed by re-irradiation over mastectomy alone for women with IBTR using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the evidence to decision framework. The following outcomes were identified by the panel: locoregional control, metastasis-free survival, overall survival, and cancer-specific survival; acute and late toxicity, specific late toxicity, second locoregional tumor, and death related to treatment. An Embase and PubMed literature search was performed by two independent authors. Five retrospective observational studies were eligible for inclusion in the present analysis. According to the reports in the literature and our analysis, the advantages of second quadrantectomy and re-irradiation (re-QUART) outweigh its side effects, with overall good rates of survival and adequate toxicity without increasing costs. Given the very low level of evidence, the panel stated that a second BCS plus re-irradiation can be considered as an alternative to salvage mastectomy for selected patients with IBTR

Treatment of muscle-invasive bladder cancer in patients without comorbidities and fit for surgery: Trimodality therapy vs radical cystectomy. Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Aim: To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC). Material and methods: Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made. Results: Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72-77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC. Conclusions: TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery

Adjuvant radiotherapy and radioiodine treatment for locally advanced differentiated thyroid cancer: systematic review and meta-analysis

Background: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated. Methods: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity. Results: Locoregional control was improved by EBRT while no considerable toxicity impact was reported. Conclusion: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting