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Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). CheckMate 141 was a randomised, open-label, phase 3 trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who progressed within 6 months after platinum-based chemotherapy. Patients were randomly assigned (2:1) to nivolumab 3 mg/kg every 2 weeks (n=240) or investigator's choice (n=121) of methotrexate (40–60 mg/m2 of body surface area), docetaxel (30–40 mg/m2), or cetuximab (250 mg/m2 after a loading dose of 400 mg/m2) until disease progression, intolerable toxicity, or withdrawal of consent. On Jan 26, 2016, the independent data monitoring committee reviewed the data at the planned interim analysis and declared overall survival superiority for nivolumab over investigator's choice therapy (primary endpoint; described previously). The protocol was amended to allow patients in the investigator's choice group to cross over to nivolumab. All patients not on active therapy are being followed for survival. As an exploratory endpoint, PROs were assessed at baseline, week 9, and every 6 weeks thereafter using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 (QLQ-C30), the EORTC head and neck cancer-specific module (EORTC QLQ-H&N35), and the three-level European Quality of Life–5 Dimensions (EQ-5D) questionnaire. Differences within and between treatment groups in PROs were analysed by ANCOVA among patients with baseline and at least one other assessment. All randomised patients were included in the time to clinically meaningful deterioration analyses. Median time to clinically meaningful deterioration was analysed by Kaplan-Meier methods. CheckMate 141 was registered with ClinicalTrials.org, number NCT02105636. Patients were enrolled between May 29, 2014, and July 31, 2015, and subsequently 361 patients were randomly assigned to receive nivolumab (n=240) or investigator's choice (n=121). Among them, 129 patients (93 in the nivolumab group and 36 in the investigator's choice group) completed any of the PRO questionnaires at baseline and at least one other assessment. Treatment with nivolumab resulted in adjusted mean changes from baseline to week 15 ranging from −2·1 to 5·4 across functional and symptom domains measured by the EORTC QLQ-C30, with no domains indicating clinically meaningful deterioration. By contrast, eight (53%) of the 15 domains in the investigator's choice group showed clinically meaningful deterioration (10 points or more) at week 15 (change from baseline range, −24·5 to 2·4). Similarly, on the EORTC QLQ-H&N35, clinically meaningful worsening at week 15 was seen in no domains in the nivolumab group and eight (44%) of 18 domains in the investigator's choice group. Patients in the nivolumab group had a clinically meaningful improvement (according to a difference of 7 points or greater) in adjusted mean change from baseline to week 15 on the EQ-5D visual analogue scale, in contrast to a clinically meaningful deterioration in the investigator's choice group (7·3 vs −7·8). Differences between groups were significant and clinically meaningful at weeks 9 and 15 in favour of nivolumab for role functioning, social functioning, fatigue, dyspnoea, and appetite loss on the EORTC QLQ-C30 and pain and sensory problems on the EORTC QLQ-H&N35. Median time to deterioration was significantly longer with nivolumab versus investigator's choice for 13 (37%) of 35 domains assessed across the three questionnaires. In this exploratory analysis of CheckMate 141, nivolumab stabilised symptoms and functioning from baseline to weeks 9 and 15, whereas investigator's choice led to clinically meaningful deterioration. Nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of investigator's choice in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck. In view of the major unmet need in this population and the importance of maintaining or improving quality of life for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, these data support nivolumab as a new standard-of-care option in this setting. Bristol-Myers Squibb.

Background The lower rectum close to the dentate line has distinct characteristics, making endoscopic submucosal dissection (ESD) of tumors challenging. We assessed clinical outcomes of ESD for such patients with hemorrhoids. Methods Sixty-four patients (mean age, 68 years) underwent ESD for anorectal tumors close to the dentate line. We divided patients into those with (Group A, 45 patients) and without hemorrhoids (Group B, 19 patients). We examined en bloc and histological en bloc resection rates, procedure time, complication rates, and postoperative prognosis after ESD. Results The mean tumor size was 43 mm. Histologic diagnoses were adenoma (42 %, 27/64), carcinoma in situ (44 %, 28/64), and T1 carcinoma (14 %, 9/64). There was no significant difference in en bloc resection (93 %, 42/45 vs. 95 %, 18/19) or postoperative bleeding rates (16 %, 7/45 vs. 11 %, 2/19) between Groups A and B, respectively. The mean procedural durations were 120 and 124 min, respectively, in Groups A and B. No perforations occurred. There was no significant difference in postoperative anal pain rate between Groups A (18 %, 8/45) and B (16 %, 3/19), and it resolved within a few days in all cases. There was one case of stricture in Group B. Two patients with T1 carcinoma underwent additional surgery, one underwent chemotherapy, and five had no additional treatment. No recurrence occurred during the follow-up period of 38 months. Conclusions ESD is safe and effective for anorectal tumors close to the dentate line in patients with hemorrhoids.

ObjectivesWalking is an adaptable, inexpensive and accessible form of physical activity. However, its impact on quality of life (QoL) and symptom severity in people with advanced cancer is unknown. This study aimed to assess the feasibility and acceptability of a randomised controlled trial (RCT) of a community-based walking intervention to enhance QoL in people with recurrent/metastatic cancer.DesignWe used a mixed-methods design comprising a 2-centre RCT and nested qualitative interviews.ParticipantsPatients with advanced breast, prostate, gynaecological or haematological cancers randomised 1:1 between intervention and usual care.InterventionThe intervention comprised Macmillan's ‘Move More’ information, a short motivational interview with a recommendation to walk for at least 30 min on alternate days and attend a volunteer-led group walk weekly.OutcomesWe assessed feasibility and acceptability of the intervention and RCT by evaluating study processes (rates of recruitment, consent, retention, adherence and adverse events), and using end-of-study questionnaires and qualitative interviews. Patient-reported outcome measures (PROMs) assessing QoL, activity, fatigue, mood and self-efficacy were completed at baseline and 6, 12 and 24 weeks.ResultsWe recruited 42 (38%) eligible participants. Recruitment was lower than anticipated (goal n=60), the most commonly reported reason being unable to commit to walking groups (n=19). Randomisation procedures worked well with groups evenly matched for age, sex and activity. By week 24, there was a 45% attrition rate. Most PROMs while acceptable were not sensitive to change and did not capture key benefits.ConclusionsThe intervention was acceptable, well tolerated and the study design was judged acceptable and feasible. Results are encouraging and demonstrate that exercise was popular and conveyed benefit to participants. Consequently, an effectiveness RCT is warranted, with some modifications to the intervention to include greater tailoring and more appropriate PROMs selected.Trial registration numberISRCTN42072606.

Systemic therapy using bone-seeking radiopharmaceuticals has clear advantages for the treatment of multisite metastatic pain. Evidence supporting the use of beta-particle, electron, and alpha-particle-emitting radiopharmaceuticals is reviewed here. Appropriate patient selection relies on correlating clinical symptoms with focal abnormalities on conventional bone scintigraphy. Time to symptom relief and response duration vary with the physical half-life and dose rate of the radionuclide used, offering the opportunity to tailor radiopharmaceutical choice to individual patient circumstances. Toxicity is limited to temporary myelosuppression, governed by the administered activity and underlying bone marrow reserve. Optimal responses are achieved in patients with a modest skeletal tumor burden, suggesting that targeted therapy should be considered early in the management of bone metastases. The development of reliable dosimetric models will facilitate patient-specific prescribing to deliver enhanced symptom response within acceptable toxicity limits. It is likely that targeted therapy will be most effective in the context of multimodality tumor management. Further research is required to examine the potential of radionuclides in combination with external-beam irradiation, bisphosphonates, or chemotherapy. This approach might allow targeted therapy to progress beyond symptom palliation to early intervention for survival gain.

Locoregional recurrence negatively impacts both long‐term survival and quality of life for several malignancies. For appropriate‐risk patients with an isolated, resectable, local recurrence, surgery represents the only potentially curative therapy. However, oncologic outcomes remain inferior for patients with locally recurrent disease even after macroscopically complete resection. Unfortunately, these operations are often extensive, with significant perioperative morbidity and mortality. This review highlights selected malignancies (mesothelioma, sarcoma, lung cancer, breast cancer, rectal cancer, and peritoneal surface malignancies) in which surgical resection is a key treatment modality and local recurrence plays a significant role in overall oncologic outcome with regard to survival and quality of life. For each type of cancer, the current, state‐of‐the‐art treatment strategies and their outcomes are assessed. The need for additional therapeutic options is presented given the limitations of the current standard therapies. New and emerging treatment modalities, including polymer films and nanoparticles, are highlighted as potential future solutions for both prevention and treatment of locally recurrent cancers. Finally, the authors identify additional clinical and research opportunities and propose future research strategies based on the various patterns of local recurrence among the different cancers.

Background There is a significant number of long-term breast cancer survivors in Germany. However, research on the psychological challenges of cancer survivors is limited. This analysis describes prevalence, development and determinants of depression and anxiety 5 to 6 years after diagnosis and identifies predictors for an increase of anxiety and depression over time. Methods Data from 164 women was collected by survey and tumour documentation during post-operative hospital stay, 40 weeks and 5 to 6 years after diagnosis. Anxiety and depression were measured by the Hospital Anxiety and Depression Scale. Sankey-diagrams were created for visual presentation of prevalence over time. Logistic and linear regression models were calculated to identify determinants of anxiety and depression. Results Respondents had higher levels of depression and anxiety 5 to 6 years than 40 weeks after the diagnosis. Lower vocational status and having children were associated with depression, surgery type was correlated with anxiety, and age, as well as comorbidities, were predictors for both anxiety and depression 5 to 6 years after diagnosis. An increase of depression over time was more likely when having children and comorbidities. An increase in anxiety was less likely after cancer recurrence. Conclusions Findings highlight that anxiety and depression are relevant burdens for breast cancer survivors in Germany. Several sociodemographic and clinical predictors are identified. There is need for psychosocial support after acute treatment and in the long-term. Research on psychological burdens of long-term breast cancer survivors in the identified vulnerable groups is needed.

ObjectiveThe association between sarcopenia and prognosis in patients with platinum-resistant recurrent ovarian cancer remains unclear. This study investigated whether sarcopenia is a prognostic factor in patients with platinum-resistant recurrent ovarian cancer.MethodsA total of 52 patients diagnosed with platinum-resistant recurrent ovarian cancer who had undergone non-platinum chemotherapy at our institution formed our study population. Body composition and clinicopathological data of these patients were collected retrospectively. Abdominal computed tomography (CT) scans obtained at the time of platinum-resistant recurrent ovarian cancer diagnosis were used to measure the cross-sectional area of skeletal muscles at L3 level. These values were corrected for height to calculate the skeletal muscle index, and accordingly sarcopenia was defined. Overall survival was defined as the primary outcome of the study. The impact of sarcopenia on overall survival was assessed using Cox proportional hazards regression models with inverse probability weighting of treatment based on propensity scores and log-rank tests.ResultsThe median patient age was 63 years (IQR: 53–71). The most common International Federation of Gynecology and Obstetrics (FIGO) 2018 stage was stage III (50%) and the most common histology was serous or adenocarcinoma (67.3%). The optimal cut-off value of skeletal muscle index was 35.6 cm2/m2, which was calculated using the data of 21 patients with sarcopenia and 31 without sarcopenia. Sarcopenia was significantly associated with shorter overall survival (HR 1.93; 95% CI 1.06–3.49; p=0.03). Subgroup analysis based on patient attributes and prognostic factors suggested a consistent prognostic impact of sarcopenia. Sarcopenia was identified as a significant risk factor, particularly in patients who had higher CA125 levels (HR, 2.47; 95% CI, 1.07 to 5.69; p=0.034) and a higher neutrophil-to-lymphocyte ratio (HR, 2.92; 95% CI, 1.02 to 8.31; p=0.045).ConclusionSarcopenia significantly shortened the overall survival of patients with platinum-resistant recurrent ovarian cancer.

Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression‐free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2–47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73–2.17, P  < 0.001), higher risk of tumor recurrence (HR: 1.75, 95% CI 1.56–1.96, P  < 0.001), lower objective response rate (OR: 0.37 95% CI 0.17–0.81, P  = 0.012), and more drug-related adverse events (OR: 2.23, 95% CI 1.17–4.28, P  = 0.015) in HCC patients. The subgroup analyses revealed that the OS of patients at the early stage of tumor was more severely affected by sarcopenia than for patients at other stages. Moreover, the presence of cirrhosis and Child Pugh class B increased the hazard of mortality from sarcopenia. This study has shown that sarcopenia is highly associated with poor prognosis in HCC patients. In addition, cirrhosis and poor liver functional reserve increase the danger of sarcopenia. OS was more impaired in HCC patients with sarcopenia at early stage of tumor than at other tumor stages.

Background Traditionally, surgical treatment is recommended for right-sided colonic cancer obstruction (RCCO); however, the literature comparing surgical or non-surgical procedures is lacking. Methods Patients included in this study were divided into two groups: one group received elective surgery after self-expanding metal stent (SEMS) placement, i.e., the bridge to surgery (BTS) group, and one group received emergency surgery (ES). Results Thirty-five patients were included in the BTS group and 60 patients underwent ES. The technical and clinical success rates for SEMS placement were 100% and 88.6%, respectively, while the short-term complication rates were 51.4% and 33.3% for the BTS and ES groups, respectively ( p  = 0.082). Overall, 2.9% and 3.3% of postoperative deaths occurred in the BTS and ES groups ( p  = 1.000). The 1-year overall survival (OS) rates were 91.4% and 88.3% ( p  = 0.840), 3-year OS rates were 85.7% and 81.7% ( p  = 0.860), and 5-year OS rates were 82.9% and 76.7% ( p  = 0.620) in the BTS and ES groups, respectively. No tumor recurrence was found in the BTS group but seven recurrences were found in the ES group (11.7%) [ p  = 0.091]. Laparoscopic surgery was chosen by 42.9% of patients in the BTS group and 26.7% of patients in the ES group ( p  = 0.104); however, the length of hospital stay ( p  = 0.001) was longer in the BTS group. Conclusions In the two groups, no differences were found in terms of postoperative complications and mortality as well as OS. The BTS group preferred to perform laparoscopic surgery and the technical success rate of stenting was high, therefore SEMS for RCCO was considered safe and feasible.

Background Cutaneous radiation-associated angiosarcoma of the breast (CRAASBr) is a rare complication of radiation therapy (RT) administered for primary breast cancer treatment. Although case series have provided clinical and histological descriptions of this disease, to our knowledge, none have identified trends in presentation and treatments that may contribute to outcomes. Methods Demographic, clinical, histopathologic, and outcomes data for all patients presenting with CRAASBr for treatment or consultation at our institution from 1987 to 2009 were reviewed. Results We identified 33 patients (median age at CRAASBr presentation 71.3 years, range 43.1–87.2 years; median latency period 73.5 months, range 39.6–148.5 months). The most common presentation was breast skin ecchymosis (55 %). In four patients, initial biopsy demonstrated atypical vascular lesions suspicious for, but not diagnostic of, angiosarcoma. All patients underwent mastectomy. Median local recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) rates were 18.2, 13.0, and 48.5 months, respectively. Patients who underwent resection of all irradiated breast skin as part of the mastectomy trended toward a better median LRFS (80.8 vs. 10.0 months, p  = 0.065), RFS (72.6 vs. 10.0 months, p  = 0.098), and OS (not achieved vs. 29.0 months, p  = 0.054). Conclusions CRAASBr is a potentially devastating consequence of RT for breast cancer, with poor LRFS, RFS, and OS rates. Patients with ecchymotic skin lesions require biopsy. Atypical vascular lesions require careful evaluation to rule out CRAASBr. If the diagnosis is confirmed, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin should be performed.