Search

Simple Summary Treatment of small HER2+ breast cancers with adjuvant Trastuzumab is still controversial. This study aims to measure the effect of Trastuzumab in early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which factors most affect the prognosis of small HER2+ tumors. We retrospectively selected and reviewed 100 HER2+ pT1mic-pT1a breast cancer patients with a median follow-up of 86 months. In our study the primary outcome was the disease recurrence rate, which appeared to be significantly lower among patients who received adjuvant Trastuzumab. Among the patients who did not receive adjuvant Trastuzumab, HR− HER2+ tumors showed a risk seven times higher of relapse. The results of our study indicate that adjuvant Trastuzumab reduces the risk of developing a disease recurrence even in small HER2+ tumors. Adjuvant targeted therapy should be considered in patients with HR− HER2+ tumors, the category with the highest risk of recurrence. Abstract The treatment with adjuvant Trastuzumab in patients diagnosed with HER2+ small breast cancers is controversial: limited prospective data from randomized trials is available. This study aims to measure the effect of Trastuzumab in the early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which are the factors that most affect the prognosis of small HER2+ tumors. One hundred HER2+ pT1mic-pT1a breast cancer patients who were treated in three Turin Breast Units between January 1998 and December 2018 were retrospectively selected and reviewed. Trastuzumab was administered to 23 patients. Clinicopathological features and disease-free survival (DFS) were compared between different subgroups. The primary outcome was the disease recurrence rate. Median follow-up time was 86 months. Compared to pT1a tumors, pT1mic lesions had a higher tumor grade (84% of pT1mic vs. 55% of pT1a; p = 0.003), a higher Ki-67 index (81% vs. 46%; p = 0.007) and were more frequently hormone receptor (HR) negative (69% vs. 36%, p = 0.001). Disease recurrence rate was significantly lower among patients who received adjuvant Trastuzumab (p = 0.02), with this therapy conferring an 85% reduction in the risk of relapse (HR 0.15; p = 0.02). Among the patients who did not receive adjuvant Trastuzumab, the only factor significantly associated with an increased risk of developing a recurrence was the immunohistochemical (IHC) subtype: in fact, HR− HER2+ tumors showed a risk seven times higher of relapsing (HR 7.29; p = 0.003). Adjuvant Trastuzumab appears to reduce the risk of disease recurrence even in small HER2+ tumors. The adjuvant targeted therapy should be considered in patients with HR− HER2+ tumors since they have the highest risk of recurrence, independently from size and grade.

Simple Summary Patients with prostate cancer often experience pain, fatigue and other negative symptoms that can lead to poorer quality of life. Enzalutamide is a prostate cancer therapy that is effective across the disease continuum from early-state cancer patients through to patients with metastatic castration-resistant disease. In this study, we evaluated how enzalutamide impacts patients’ quality of life. We found that patients with early disease maintained low pain levels and symptom-related burden when treated with enzalutamide or with a control treatment, and that patients with advanced disease who received enzalutamide experienced mitigated negative impacts compared to controls. Furthermore, it took longer for patients treated with enzalutamide to report experiencing a reduction in quality of life, and this was most pronounced for patients with advanced cancer. Enzalutamide can be tolerated by patients with early or advanced prostate cancer and delays both disease progression and the associated deterioration of quality of life. Abstract This review examines the impact of treatment with enzalutamide on health-related quality of life (HRQoL) in prostate cancer patients across the disease continuum based on pivotal clinical trials. We assessed the effect of enzalutamide on pain, symptom burden and overall HRQoL from randomized controlled trials. Patient experience was evaluated in men with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC) (pre-chemotherapy and post-chemotherapy). Patients across the disease continuum reported a generally positive status at baseline, with relatively low levels of pain and impairment due to cancer-related symptoms and high HRQoL. For patients with earlier-state prostate cancer, pain and symptom-related burden were low at study entry and remained so, regardless of whether patients received enzalutamide or control treatment. Patients with more advanced disease reported mitigation in pain and symptom burden while receiving treatment with enzalutamide. Enzalutamide was observed to slow deterioration of overall HRQoL most for patients with nmCRPC or mCRPC (statistical significance for between-group difference in median time to deterioration: mHSPC (confirmed) p = 0.2998; nmCRPC (confirmed) p = 0.0044; mCRPC (unconfirmed) p < 0.0001). Across the prostate cancer continuum, enzalutamide is well-tolerated and delays the negative impact that disease progression has on quality of life.

Simple Summary Contrary to other head and neck subsites, oropharyngeal squamous cell carcinoma (OPSCC) has shown a considerable increase in incidence over the past 20 years. This growing incidence is largely due to the increasing place of human papillomavirus (HPV)-related tumors. HPV-positive and HPV-negative OPSCC are two distinct entities with considerable differences in terms of treatment response and prognosis. However, there are no specific recommendations yet in the therapeutic management of OPSCC patients according to their tumor HPV-status. The aim of this review is therefore to discuss the therapeutic management of patients with OPSCC and the impact of HPV status on treatment selection. Abstract Since there is no published randomized study comparing surgical and non-surgical therapeutic strategies in patients with oropharyngeal squamous cell carcinoma (OPSCC), the therapeutic management of these patients remains highly controversial. While human papillomavirus (HPV)-positive and HPV-negative OPSCC are now recognized as two distinct diseases with different epidemiological, biological, and clinical characteristics, the impact of HPV status on the management of OPSCC patients is still unclear. In this review, we analyze the current therapeutic options in patients with OPSCC, highlighting the most recent advances in surgical and non-surgical therapies, and we discuss the impact of HPV status on the therapeutic strategy.

Simple Summary Even though up to 20% of patients with cancer eventually develop brain metastases (BM), most clinical trials have historically forbidden the enrolment of individuals with BM. The reasons for this practice include considerations regarding safety and efficacy, but there is a pressing need to verify whether new treatments also work for patients with BM. In this article, we assessed the literature on breast cancer and found that there has been an increase over time of trials allowing enrolment of breast cancer patients with BM, and that when the results for these patients were reported separately, they tended to go in the same direction as those observed for all patients. Our results suggest that further efforts are needed to increase the assessment of new treatments for patients with BM. Abstract Background: Although brain metastases (BM) affect 5% of all breast cancer patients and 14% of those with metastatic disease, patients with BM are often excluded from participation in clinical trials. We conducted a structured assessment of the contemporary restrictions to enrolment of, and results for, patients with BM in phase 3 trials published over a period of 23 years in advanced breast cancer. Methods: We used PubMed to search for completed randomized trials published between 01/98 and 12/20. For all eligible trials, two authors independently abstracted data on general characteristics of the studies and detailed information on patient eligibility regarding the presence of BM. Results: We analyzed 210 trials, which enrolled 92,409 eligible patients. Of that total, 162 (77.1%) publications explicitly mentioned eligibility criteria related to the presence of BM and 75 (35.7%) trials reportedly allowed patients with BM, usually with restrictions related to prior brain treatment or stability of lesions. There was a significant increase over time in the percentages of trials allowing patients with BM (p < 0.001), and these trials were more frequently dedicated to HER2-positive or triple-negative disease (p = 0.001). Only 11 trials reported separate results for patients with BM at baseline. The direct treatment activity on BM was usually not reported, although in subgroup analyses the treatment effect in relative terms was usually better among patients with BM than in overall populations. Conclusion: Nearly 36% of phase 3 trials in advanced breast cancer over a 23-year period allowed patients with BM, and this practice is increasing over time. More research is needed to establish the activity of current and promising therapies in patients with BM.

Simple Summary Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are 60 years or older and tend to have a poor prognosis. Evidence to guide and optimize treatment choices for these vulnerable patients is limited. We performed a scoping review to identify and describe all relevant clinical studies investigating chemotherapies and combinations of chemotherapies (including high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT)) in elderly PCNSL patients. In total, we identified six randomized controlled trials, 26 prospective and 24 retrospective studies (with/without control group). While most studies investigated protocols based on ‘conventional’ chemotherapy treatment, data evaluating HCT-ASCT in the elderly were scarce, and the generalizability of the only RCT published is questionable. Considering the poor prognosis of these patients and their need for more effective treatment options, a thoroughly planned randomized controlled trial comparing HCT-ASCT with ‘conventional’ chemoimmunotherapy is urgently needed to evaluate the efficacy of HCT-ASCT. Abstract Background: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. Materials and Methods: We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. Results: In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Conclusions: Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment.

Background: Chronic inflammation associated with breast cancer (BC) poses a major challenge in care management and may be ameliorated by physical activity. This randomized controlled trial assessed the effects of a 12-week high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on inflammatory markers, body composition, and physical fitness in BC survivors (BCS). Methods: Forty BCS (age = 57 ± 1 years, body mass [BM] = 74.8 ± 1.5 kg, VO2peak = 20.8 ± 2.1 mL·kg−1·min−1) were randomly assigned to three groups: HIIT (n = 15), MICT (n = 15), or control (CON, n = 15). The intervention groups (HIIT and MICT) performed their respective exercise protocols on a cycle ergometer 3 days/week for 12 weeks while the CON group maintained their current lifestyle. Baseline and post-intervention assessments included body composition (BM, fat mass (FM), lean mass (LM)), physical fitness (VO2peak, lower body strength (LBS), upper body strength (UBS)), and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), leptin, and adiponectin. Results: Both intervention groups significantly (p &lt, 0.05) decreased BM (HIIT = −1.8 kg, MICT = −0.91 kg), FM (HIIT = −0.81 kg, MICT = −0.18 kg), TNF-α (HIIT = −1.84 pg/mL, MICT = −0.99 pg/mL), IL-6 (HIIT = −0.71 pg/mL, MICT = −0.36 pg/mL), leptin (HIIT = −0.35 pg/mL, MICT = −0.16 pg/mL) and increased VO2peak (HIIT = 0.95 mL·kg−1·min−1, MICT = 0.67 mL·kg−1·min−1), LBS (HIIT = 2.84 kg, MICT = 1.53 kg), UBS (HIIT = 0.53 kg, MICT = 0.53 kg), IL-10 (HIIT = 0.63 pg/mL, MICT = 0.38 pg/mL), and adiponectin (HIIT = 0.23 ng/mL, MICT = 0.1 ng/mL) compared to baseline. The changes in BM, FM, TNF-α, leptin, and LBS were significantly greater in HIIT compared to all other groups. Conclusions: Our findings indicate that compared to the often-recommended MICT, HIIT may be a more beneficial exercise therapy for the improvement of inflammation, body composition and LBS in BCS, and consequently, merits long-term study

Simple Summary Bladder cancer is one of the most common malignancies in the United States with a majority of patients diagnosed with non-muscle invasive bladder cancer (NMIBC). Despite early detection and regular surveillance of most cases, recurrence and progression rates remain high. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Through the collection of prospective and randomized controlled trials, we demonstrated that tumor resection with either PDD and NBI exhibited greater diagnostic sensitivity compared to WLC alone. Our findings underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC. Abstract Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.

Comments: We have some additional considerations about the recent published article by Perri et al [...]

Simple Summary This is a Phase II randomized controlled trial conducted with the aim of investigating whether the use of Electrochemotherapy after neoadjuvant therapy (ECT) and before surgery in patients with major clinical response allows for a more conservative surgical approach in patients with Locally Advanced Rectal Cancer (LARC) in comparison with the control group that will not receive ECT. The treatment response, in both the control arm and in the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision. Abstract Background: Currently, 45–55% of rectal cancer patients receive preoperative chemo- radio-therapy for Locally Advanced Rectal Cancer (LARC). The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. Objective: To evaluate the increase of the complete response rate after neoadjuvant treatment in LARC and to spare organ function due to total mesorectal excision (TME). Patients and Methods: This is a Phase II randomized controlled trial enrolling 70 patients that will be developed in two stages. In the first step, 28 patients will be enrolled: 14 of these will receive ECT for four weeks after neo-adjuvant treatment and then local excision (treatment group) and 14 patients will receive neo-adjuvant treatment and then local excision (control group). If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients. The treatment response. in both the control arm and the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.

Purpose/Objective: The standard treatment for localized low-risk breast cancer is breast-conserving surgery, followed by adjuvant radiotherapy and appropriate systemic therapy. As the majority of local recurrences occur at the site of the primary tumor, numerous trials have investigated partial-breast irradiation (PBI) instead of whole-breast treatment (WBI) using a multitude of irradiation techniques and fractionation regimens. This meta-analysis addresses the impact on disease-specific endpoints, such as local and regional control, as well as disease-free survival of PBI compared to that of WBI in published randomized trials. Material and Methods: We conducted a systematic literature review and searched for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was based on the published event rates and the effect sizes for available oncological endpoints of at least two trials reporting on them. We evaluated in-breast tumor recurrences (IBTR), local recurrences at the primary site and elsewhere in the ipsilateral breast, regional recurrences (RR), distant metastasis-free interval (DMFI), disease-free survival (DFS), contralateral breast cancer (CBC), and second primary cancer (SPC). Furthermore, we aimed to assess the impact of different PBI techniques and subgroups on IBTR. We performed all statistical analyses using the inverse variance heterogeneity model to pool effect sizes. Results: For the intended meta-analysis, we identified 13 trials (overall 15,561 patients) randomizing between PBI and WBI. IBTR was significantly higher after PBI (OR = 1.66, CI-95%: 1.07–2.58, p = 0.024) with an absolute difference of 1.35%. We detected significant heterogeneity in the analysis of the PBI technique with intraoperative radiotherapy resulting in higher local relapse rates (OR = 3.67, CI-95%: 2.28–5.90, p &lt, 0.001). Other PBI techniques did not show differences to WBI in IBTR. Both strategies were equally effective at the primary tumor site, but PBI resulted in statistically more IBTRs elsewhere in the ipsilateral breast. IBTRs after WBI were more likely to be located at the primary tumor bed, whereas they appeared equally distributed within the breast after PBI. RR was also more frequent after PBI (OR = 1.75, CI-95%: 1.07–2.88, 0.001), yet we did not detect any differences in DMFI (OR = 1.08, CI-95%: 0.89–1.30, p = 0.475). DFS was significantly longer in patients treated with WBI (OR = 1.14, CI-95%: 1.02–1.27, p = 0.003). CBC and SPC were not different in the test groups (OR = 0.81, CI-95%: 0.65–1.01, p = 0.067 and OR = 1.09, CI-95%: 0.85–1.40, p = 0.481, respectively). Conclusion: Limiting the target volume to partial-breast radiotherapy appears to be appropriate when selecting patients with a low risk for local and regional recurrences and using a suitable technique.

Simple Summary In general, 5–20% of all cancers are due to pathogenic variants in cancer genes that are passed down in the family. It is recommended that blood relatives of individuals with such a pathogenic variant have genetic testing, to identify if they also carry the same variant. This information will help their healthcare providers to make individualized cancer screening and prevention plans. However, only around 30% of at-risk relatives have genetic testing, presumably due to a lack of communication about inherited cancer genes among family members. In this paper, we identified interventions that were designed to improve family communication about hereditary cancer and/or genetic testing among at-risk relatives for two common hereditary cancer syndromes. We analyzed the components of these interventions and synthesized outcomes with statistical methods. Although we identified 14 eligible studies, there are still many unanswered questions about clinical and research implications with diverse samples to be addressed in future studies. Abstract Evidence-based guidelines recommend cascade genetic testing of blood relatives of known Hereditary Breast and Ovarian Cancer (HBOC) or Lynch Syndrome (LS) cases, to inform individualized cancer screening and prevention plans. The study identified interventions designed to facilitate family communication of genetic testing results and/or cancer predisposition cascade genetic testing for HBOC and LS. We conducted a systematic review and meta-analysis of randomized trials that assessed intervention efficacy for these two outcomes. Additional outcomes were also recorded and synthesized when possible. Fourteen articles met the inclusion criteria and were included in the narrative synthesis and 13 in the meta-analysis. Lack of participant blinding was the most common risk of bias. Interventions targeted HBOC (n = 5); both HBOC and LS (n = 4); LS (n = 3); or ovarian cancer (n = 2). All protocols (n = 14) included a psychoeducational and/or counseling component. Additional components were decision aids (n = 4), building communication skills (n = 4), or motivational interviewing (n = 1). The overall effect size for family communication was small (g = 0.085) and not significant (p = 0.344), while for cascade testing, it was small (g = 0.169) but significant (p = 0.014). Interventions show promise for improving cancer predisposition cascade genetic testing for HBOC and LS. Future studies should employ family-based approaches and include racially diverse samples.

Simple Summary The most effective and safest approach for the treatment of advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) remains unknown. A systematic review was done to clarify this point. A network meta-analysis was used to overcome the multiarm problem. Our study confirmed that somatostatin analogs (SSAs) alone remain the best choice for well-differentiated GEP–NENs. 177Lu-Dotatate plus SSA is a valid alternative for midgut NENs since it has been shown to be slightly more efficacious but yielding a higher risk for toxicity than SSAs. Abstract Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP–NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3–4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one 177Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. 177Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), 177Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with 177Lu-Dotatate.

Simple Summary Pancreatic adenocarcinoma is predicted to be the 2nd cause of death by cancer in Western Countries in 2023. Most patients are diagnosed at an advanced stage for which chemotherapy is the main treatment. In this study we developed through an innovative approach, a simple nine genes blood RNA-based signature that predicts sensitivity to gemcitabine, one of the main regimens in combination with nab-paclitaxel or alone in less fit patients. Abstract Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second cause of cancer death by 2022. For nearly 80% of patients, diagnosis occurs at an advanced, nonsurgical stage, making such patients incurable. Gemcitabine is still an important component in PDAC treatment and is most often used as a backbone to test new targeted therapies and there is, to date, no routine biomarker to predict its efficacy. Samples from a phase III randomized trial were used to develop through a large approach based on blood-based liquid biopsy, transcriptome profiling, and machine learning, a nine gene predictive signature for gemcitabine sensitivity. Patients with a positive test (41.6%) had a significantly longer progression free survival (PFS) (3.8 months vs. 1.9 months p = 0.03) and a longer overall survival (OS) (14.5 months vs. 5.1, p < 0.0001). In multivariate analyses, this signature was independently associated with PFS (HR = 0.5 (0.28–0.9) p = 0.025) and OS (HR = 0.39 (0.21–0.7) p = 0.002).

For the treatment of early and locally advanced glottic laryngeal cancer, multiple strategies are available. These are pursued and supported by different levels of evidence, but also by national and institutional traditions. The purpose of this review article is to compare and discuss the current evidence supporting different loco-regional treatment approaches in early and locally advanced glottic laryngeal cancer. The focus is kept on randomized controlled trials, meta-analyses, and comparative retrospective studies including the treatment period within the last twenty years (≥ 1999) with at least one reported five-year oncologic and/or functional outcome measure. Based on the equipoise in oncologic and functional outcome after transoral laser surgery and radiotherapy, informed and shared decision-making with and not just about the patient poses a paramount importance for T1-2N0M0 glottic laryngeal cancer. For T3-4aN0-3M0 glottic laryngeal cancer, there is an equipoise regarding the partial/total laryngectomy and non-surgical modalities for T3 glottic laryngeal cancer. Patients with extensive and/or poorly functioning T4a laryngeal cancer should not be offered organ-preserving chemoradiotherapy with salvage surgery as a back-up plan, but total laryngectomy and adjuvant (chemo) radiation. The lack of high-level evidence comparing contemporary open or transoral robotic organ-preserving surgical and non-surgical modalities does not allow any concrete conclusions in terms of oncological and functional outcome. Unnecessary tri-modality treatments should be avoided. Instead of offering one-size-fits-all approaches and over-standardized rigid institutional strategies, patient-centered informed and shared decision-making should be favored.

Glioblastoma (GBM) is the most common high-grade primary brain tumor in adults. Standard multi-modality treatment of glioblastoma with surgery, temozolomide chemotherapy, and radiation results in transient tumor control but inevitably gives way to disease progression. The need for additional therapeutic avenues for patients with GBM led to interest in anti-angiogenic therapies, and in particular, bevacizumab. We sought to determine the efficacy of bevacizumab as a treatment for newly diagnosed GBM. We conducted a literature search using the PubMed database and Google Scholar to identify randomized controlled trials (RCTs) since 2014 investigating the safety and efficacy of bevacizumab in the treatment of adult patients (18 years and older) with newly diagnosed GBM. Only Level Ι data that reported progression-free survival (PFS) and overall survival (OS) were included for analysis. Random effects meta-analyses on studies with newly diagnosed glioblastoma were conducted in R to estimate the pooled hazard ratio (HR) for PFS and OS. Six RCTs met requirements for meta-analysis, revealing a pooled estimate of PFS HR suggesting a 33% decreased risk of disease progression (HR 0.67, 95% CI, 0.58−0.78; p < 0.001) with bevacizumab therapy, but no effect on OS (HR = 1, 95% CI, 0.85−1.18; p = 0.97). A pooled estimate of the mean difference in OS months of −0.13 predicts little difference in time of survival between treatment groups (95% CI, −1.87−1.61). The pooled estimate for the mean difference in PFS months was 2.70 (95% CI, 1.89−3.50; p < 0.001). Meta-analysis shows that bevacizumab therapy is associated with a longer PFS in adult patients with newly diagnosed glioblastoma, but had an inconsistent effect on OS in this patient population.

Background: Improving patients&rsquo, quality of life (QoL) is a principal objective of all treatment in any clinical setting, including oncology practices. Cancer-associated inflammation is implicated in disease progression and worsening of patients&rsquo, QoL. Conventional anticancer therapeutics while selectively eliminating cancerous cells, are evaded by stem cell-like cells, and associated with varying degrees of adverse effects, thus reducing patients&rsquo, QoL. This necessitates novel therapeutic approaches with enhanced efficacy, minimal or no treatment-related adverse effects, and improved QoL in patients with cancer, especially those with metastatic/advance stage disease. Methods: Sequel to our team&rsquo, s previous publication, the present study explores probable effects of Astragalus polysaccharides (PG2) on cancer-related inflammatory landscape and known determinants of QoL, as well as the probable link between the two to provide mechanistic insight. In an exploratory double blind randomized controlled trial using patients with metastatic disease (n = 23), we comparatively evaluated the therapeutic efficacy of high (500 mg) or low (250 mg) dose PG2 administered intravenously (i.v.), with particular focus on its suggested anti-inflammatory function and the probable effect of same on QoL indices at baseline, then at weeks 4 and 8 post-PG2 treatment. Results: All 23 patients with metastatic disease treated with either low or high PG2 experienced reduced pain, nausea, vomiting, and fatigue, as well as better appetite and sleep, culminating in improved global QoL. This was most apparent in the high dose group, with significant co-suppression of pro-inflammatory interleukin (IL)-1&beta, IL-4, IL-6, IL-13, IL-17, monocytes chemotactic protein (MCP)1, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), tumor growth factor (TGF)-&beta, 1, interferon (IFN)-&gamma, and immune suppressors IL-10 and IL-12. Univariate and multivariate analyses revealed that IL-1&beta, IL-13 and GM-CSF are independent prognosticators of improved QoL. Conclusion: This proof-of-concept study provides premier evidence of functional association between PG2 anti-inflammatory effects and improved QoL in patients with advanced stage cancers, laying the groundwork for future larger cohort blinded controlled trials to establish the efficacy of PG2 as adjuvant anticancer therapy in metastatic or advanced stage clinical settings.

Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate⁻high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients’ characteristics or physicians’ attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as “promising„ in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients.