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Objective: The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review assessed the strength and quality of evidence and graded the evidence derived from published meta-analyses on this subject. Data sources: MEDLINE, Embase, and the Cochrane Library were searched. Meta-analyses of observational studies and randomized trials were included. Review methods: Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: 15 meta-analyses were evaluated. The association with HPV was highly suggestive of oral (OR = 2.40, [1.87–3.07], P < 0.00001) and nasopharyngeal cancers (OR = 17.82 [11.20–28.35], P < 0.00001). Improved survival emerged only in hypopharyngeal carcinoma and was confirmed in studies in which only p16 + cancers were considered. Conclusion: HPV infection may increase the risk of oral cavity and nasopharyngeal cancer. However, the prognosis was not influenced, except in hypopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Purpose of Review: The treatment of colorectal cancer (CRC) has evolved and become more personalized during the past several years. For example, depotentiation/reduced duration of systemic therapies has proven to be beneficial in both advanced and early stages of the disease. Recent Findings: In particular, recent randomized studies of stage III and high-risk stage II CRC showed that a shorter duration (3 months), when compared to the historical 6-month comparator, provides nearly similar overall survival (OS) and disease-free survival (DFS). In the setting of advanced, inoperable CRC, a relatively short induction phase (six to eight cycles) followed by biological agents is the current standard of care in RAS wild-type (wt). versus RAS mutated cases. With regard to potentially operable stage IV disease (with the aim of converting liver metastases to operability), a relatively short number of cycles (four to six cycles) should be offered with re-staging and re-evaluation for surgery as soon as possible in most cases. For inoperable liver metastases, a relatively intensive triplet or doublet plus targeted therapy may attain conversion in some cases and may even result in cure. Rectal cancer treatment continues to be a complex disease in terms of treatment and oncological results. Recent data seem to showcase the benefits of more prolonged sequential strategies (total neoadjuvant therapy, all treatment delivered before surgery, to reduce the risk of distant metastases and local control). Summary: In recent years, different strategies regarding treatment intensity have been employed in CRC in adjuvant and metastatic setting. Introduction of triplets as first-line therapy for colon cancer and as induction phase for rectal cancer are now therapeutic options. Conversely in stage II disease or low-risk stage III resected CRC, a reduced chemotherapy length is a new standard of care. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. Material and methods: Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. Results: A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III–IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29–65 and 0.3; 95% CrIs 0.03–2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19–12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). Conclusions: This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS. [ABSTRACT FROM AUTHOR]

Introduction: Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT) according to FLOT schedule (5FU/leucovorin/oxaliplatin and docetaxel), or of concomitant chemoradiotherapy (CTRT) based on CROSS regimen. However, due to the relatively lack of direct comparisons between perioperative CT and neoadjuvant CTRT, the effectiveness of these new combinations is unknown. Therefore, we performed a network meta-analysis (NMA) to compare the efficacy of different neoadjuvant treatments for gastric and GEJ adenocarcinoma in terms of overall and disease-free survival (OS and DFS). Materials and methods: We searched MEDLINE, Embase, and Cochrane from database inception until February 1st 2022 for randomized clinical trials that enrolled adults with gastric and GEJ carcinomas and provided data about OS and/or DFS. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank (SUCRA) curve plots were produced. The primary outcome was OS, secondary endpoint DFS. Results: A total of 1247 citations were screened; 14 randomized clinical trials were included. In Bayesian comparisons, FLOT-based CT ranked as one of the better regimens with a probability of 41%, both with induction CT followed by CTRT (P = 0.45). For DFS analysis, the FLOT regimen was the preferred option (P = 0.62). Conclusions: In conclusion, this NMA adds further evidence to the optimization of treatment strategies for gastric and GEJ adenocarcinomas and confirms that incorporation of perioperative triplet-based CT improved both OS and DFS compared to surgery alone and other preoperative strategies. [ABSTRACT FROM AUTHOR]

Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil (5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26–0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45–1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role. [ABSTRACT FROM AUTHOR]

Background: Over recent years, immune checkpoint inhibitors (ICIs) have changed the clinical management and prognosis for most cancers. However, data on older patients in clinical trials are scarce. Objective: We performed a systematic review and pooled analysis of real-life studies to explore the efficacy and toxicity of ICIs in unselected older individuals in multiple tumor settings treated outside of clinical trials. Patients and Methods: We searched articles, including prospective cohort studies, observational or retrospective series, or expanded access programs, published in English from 2010 to October 2020 in PubMed, MEDLINE, the Cochrane Library, and EMBASE. We excluded hematological malignancies. Results: Forty-eight studies met the predefined criteria and were eligible for inclusion in the systematic review. We included 5524 patients. The pooled median overall survival was 8.9 (95% CI 7.3–10.5) and 14.3 (95% CI 11.3–17) months for non-small cell lung cancer (NSCLC: n = 17 studies; 95% in pretreated setting) and melanoma, respectively (n = 3). Median progression-free survival was 3.2 (95% CI 2.7–3.8) and 7.9 (95% CI 6.05–9.78) months for NSCLC and melanoma cohorts. Pooled rates of Grade 1–5 hepatitis, pneumonitis, hypothyroidism, and diarrhea were 5.3% (95% CI 3.7–7.6), 6% (95% CI 3.8–9.4), 8.3% (95% CI 5.4–12.5) and 7.6% (95% CI 5.7–10), respectively. Conclusions: Our findings suggest that ICIs could be safely administered in older individuals with comparable survival outcomes with respect to younger individuals. Future studies should include some form of geriatric assessment to improve patient stratification. [ABSTRACT FROM AUTHOR]

Objective: The human papillomavirus (HPV) is implicated in the pathogenesis of several cancers among humans. The role of HPV as one of the etiological agents in esophageal carcinogenesis is partially unknown. We assessed whether the available evidence supports the association of HPV with risk and prognosis in patients with esophageal squamous cell carcinomas (ESCCs). Design: For this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and SCOPUS were searched up to February 2021. The included studies were prospective or retrospective studies that evaluated the incidence, risk, and prognosis of HPV-16/18–related ESCCs in adult subjects. The primary outcome was the incidence rate of ESCC in HPV-16/18 carriers. Secondary outcomes included the risk of ESCCs compared with healthy HPV-16/18 carriers (expressed as odds ratios [ORs] with 95% confidence intervals [CIs]) and the survival of HPV + versus HPV- ESCCs. Results: The search identified 1649 unique citations, of which 145 met the inclusion criteria and were included in the pooled analysis (16,484 patients). The pooled HPV prevalence in ESCCs was 18.2% (95% CI 15.2–21.6%; P < 0.001). A significantly increased ESCC risk was associated with HPV infection (OR = 3.81; 95% CI 2.84–5.11; P < 0.001). Main limitation were methods of HPV detection (DNA only), race of populations included (mainly Asiatic countries) and lack of adjustment for other prognostic factors. Conclusions: The findings suggest that HPV-16/18 is detectable in about 1 on 5 cases of ESCC with different prevalences across the world. It is moderately but significantly associated with a diagnosis of ESCC. Further epidemiological studies are needed to confirm and increase the current knowledge of the subject. [ABSTRACT FROM AUTHOR]

Background: The relative risk (RR) of infection for patients treated with immune checkpoint inhibitors (ICIs) is unknown. Objectives: This study evaluated the risk of infection for patients with solid tumors undergoing ICI therapy based on a systematic review and meta-analysis. Patients and Methods: The Cochrane Library, EMBASE, and Pubmed databases were searched up to 1 December 2020. Randomized trials comparing any ICI alone, with chemotherapy (CT), or with other agents versus placebo, CT, or other agents were included. Three independent reviewers extracted the data. The primary outcome was the RR of all-grade (G) and G3–5 infections for patients receiving ICI-based treatments. Random or fixed-effect models were used according to statistical heterogeneity. Results: A total of 21,451 patients from N = 36 studies were eligible. ICIs were associated with a similar risk of all-grade infections (RR = 1.02; 95% CI 0.84–1.24; P = 0.85) versus non-ICI treatments (G1–5 events: 9.6 versus 8.3%). When the ICIs alone were compared to CT, their use was associated with 42% less risk of all-grade infections (RR = 0.58, 95% CI 0.4–0.85; P = 0.01). Compared to CT, the combination of ICIs and CT increased the risk of all-grade (RR = 1.37, 95% CI 1.23–1.53; P < 0.01) and severe infections (RR = 1.52, 95% CI 1.17–1.96; P < 0.01). In anti-PD-1, anti-PD-L1, anti-CTLA-4, monotherapy, and combination trials, the RR of all-grade infections was 0.72 (95% CI 0.49–1.05; P = 0.09), 1.18 (95% CI 0.95–1.46; P = 0.13), 1.74 (95% CI 1.13–2.67; P = 0.01), 0.97 (95% CI 0.79–1.19; P = 0.75) and 2.26 (95% CI 1.34–3.8; P < 0.01), respectively. Conclusions: Compared to CT alone, ICIs were safer and are recommended for frail patients. Conversely, CT + ICIs or ICIs combinations increased infection risk. Further studies are required to identify high-risk patients and evaluate the need for CT dose reduction or prophylactic myeloid growth factors. [ABSTRACT FROM AUTHOR]

Biliary tract cancer is an uncommon cancer in developed countries. In localized stages, surgery is the cornerstone of treatment with curative purpose. Conversely in advanced stages, chemotherapy with platinum–gemcitabine combination is the standard of care. Biliary tract cancers are a biologically heterogeneous group of malignancies, which perhaps explains the failure of targeted therapies in unselected patient populations to demonstrate benefit in advanced disease, although there are promises in selected populations (e.g. PD1/PD-L1 positive, BRAFV600E-mutated or IDH1-mutant). In view of the limited benefit of second line therapies in metastatic biliary tract cancer, various targeted agents have been tested in progressive disease. Furthermore, several ongoing trials are using next-generation sequencing of multiple genes to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially be used in pretreated disease (e.g. FGFR or IDH genes). Immunotherapy with immune checkpoint inhibitors may be interesting for patients whose tumors have programmed cell death 1 ligand 1 (PD-L1) overexpression. Ongoing and future trials will further advance our knowledge toward the optimal treatment strategy for the management of biliary tract cancer in its different stages, starting from metastatic and then reaching early stages of disease. We here provided an overview of these novel treatment strategies for advanced biliary tract cancers not amenable of curative treatment modalities. [ABSTRACT FROM AUTHOR]

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively assess prevalence/characteristics of clinically unsuspected pulmonary embolism (PE) in cancer patients undergoing follow-up chest MDCT and investigate MDCT protocol.Methods: We evaluated 1013 oncologic patients. MDCT images at 5 and 1.25 mm thickness were independently evaluated. Pulmonary artery opacification degree was assessed. Presence, level, and site of PE were reported. Type of malignancy and metastases were reported for PE-positive patients.Results: After excluding 1.4% (14/1013) of examinations due to inadequate vessel opacification, 999 patients (572 male; mean age:68 ± 12 years; range:26-93 years) entered the study. Prevalence of PE was 5%. There was significant improvement in the sensitivity for both readers in the evaluation of 1.25 mm compared to 5 mm images (46-50% to 82-92%). 30% (15/51) PE were not described by the radiologist in the prospectively issued report; 53 % (27/51) of PE were segmental, 72.5% (37/51) unilateral. The right lower lobe was the most involved (59%). 27% patients had colon cancer, 18% lung cancer. Among PE-positive patients (25 male; mean age 70 ± 10 years; range:44-87 years), 25% (13/51) had lung cancer, 15% (8/51) colon cancer.Conclusions: Thin reconstructions are essential for PE diagnosis, regardless of reader experience. Regarding oncologic patients, incidental PE diagnosis influences anticoagulation therapy.Key Points: • CT pulmonary angiography is the gold standard for PE diagnosis. • Cancer and oncological treatments are risk factors for PE. • The prevalence of unsuspected PE was 5%. • Thin reconstructions are essential for PE diagnosis regardless of reader experience. • In oncologic patients, PE diagnosis influences anticoagulation therapy. [ABSTRACT FROM AUTHOR]

Osteosarcomas of the jaws are rare mesenchymal tumors frequently diagnosed in the fourth decade of life which account for 6 % of all osteosarcomas. This study evaluated the efficacy on the patients outcome of multimodality treatment consisting of surgery, chemotherapy and radiotherapy. The records of 22 patients affected by jaw osteosarcoma treated with a combination of surgery, poly-chemotherapy and adjuvant radiotherapy in selected cases were reviewed. Response rate, progression-free survival and overall survival were evaluated. Neoadjuvant chemotherapy resulted in an overall response rate of 83.3 %, necrosis of grade I or II was obtained, respectively, in 44.4 and 55.6 % of the patients, and surgery was radical in all patients. At a median follow-up of 60 months, the 5-year progression-free survival and overall survival were 73.5 and 77.4 %, respectively. These outcome parameters significantly correlated with age at diagnosis and grade of chemotherapy-induced necrosis. A complex multimodality approach including chemotherapy and radiotherapy, along with radical surgery, can maximize the outcome of patients affected by osteosarcoma of the jaws. [ABSTRACT FROM AUTHOR]