Immune checkpoint inhibitors have revolutionized the treatment of malignancies. However, disproportionate enrollment among races and ethnicities places the generalizability of global trial results in doubt.
In this systematic review, phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers and providing subgroup analyses of Asian and non-Asian participants were included. The primary and secondary effect measures were the mean differences (MDs) in the natural logarithms of the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) between these two subgroups, respectively. We used random-effects meta-analysis to calculate the pooled ratios of HRs (i.e., exp(MD)) and implemented a meta-regression analysis to identify significant covariates.
A total of 17 and 11 trials were included in the meta-analyses of OS and PFS, respectively. These trials included 2732 (25.49%) Asian and 7000 (65.32%) non-Asian participants in the OS analysis and 1438 (22.5%) Asian and 4129 (64.61%) non-Asian participants in the PFS analysis. The pooled ratio of HRs for OS was 0.87 (95% CI: 0.76-0.99; p = 0.0391), favoring Asian participants, but no significant difference was found in PFS (pooled ratio of HRs: 0.93; 95% CI: 0.82-1.07; p = 0.2391). Both linear meta-regression analyses revealed an open-label design as a crucial covariate, which indicated more benefits for non-Asian participants.
Compared with non-Asian patients, Asian patients with advanced cancers may derive superior OS benefits from pembrolizumab. Although the results warrant further exploration, this meta-analysis provides insight into clinical research design.

The primary objective was to evaluate the safety of the anti-PD-1 antibody camrelizumab in people living with HIV (PLWH); the secondary objective was to evaluate tumor response.
From May 8, 2018, to December 10, 2021, twenty-four patients with HIV and advanced cancer as well as a CD4+ T-cell count greater than or equal to 100 cells/µL were treated with camrelizumab in daily practice. We describe the demographic characteristics, safety, and clinical course of these 24 PLWH with cancer treated with camrelizumab. Safety was assessed using the current Common Terminology Criteria for Adverse Events (CTCAE). The tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
The median number of cycles was 8 (4-26). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 24 patients, 2 (8%) complete responses and 6 (25%) partial responses were observed. 7 patients (29%) were at stable tumor status and others progressed.
Data from the present study strongly support the use of camrelizumab (monoclonal antibodies targeting the PD-1 pathway) in this population, as it appears to be a feasible approach with no deleterious effects on PLWH and tolerability and acceptable efficacy. In addition, these findings further support the inclusion of PLWH with cancer in clinical trials evaluating the safety and efficacy of ICIs on cancer.

Patients with various advanced cancers devoid of nuclear progesterone receptors (nPR) have demonstrated increased quality and length of life when treated with the PR modulator mifepristone, which likely works by interacting with membrane PRs (mPR).
Two immunomodulatory proteins are discussed that seem to play a role in cancers that proliferate whether the malignant tumor is positive or negative for the nPR. These two proteins are the progesterone receptor membrane component-1 (PGRMC-1) and the progesterone-induced blocking factor (PIBF). Both PGRMC-1 and the parent form of PIBF foster increased tumor aggressiveness, whereas splice variants of the 90 kDa form of PIBF inhibit immune response against cancer cells.
The marked clinical improvement following 200-300 mg of mifepristone is likely related to blocking PIBF. In the low dosage used, mifepristone likely acts as an agonist for PGRMC-1 protein. Mifepristone may be less effective for cancers positive for the nPR because the nPR may be protective and blocking it may have detrimental effects. Based on this hypothetical model, the development of other potential treatment options to provide even greater efficacy for treating cancer are discussed.

Shared decision-making (SDM) has been institutionally recognized as clinically effective by many Western healthcare systems. Nevertheless, it appears culturally unattractive in China, a country that adheres to Confucian familism which strongly prefers collective family decisions. This study examined this conflict and assessed the influence of Confucian familism on SDM in end-of-life (EOL) care for advanced cancer patients. Between August and November 2018, 188 EOL advanced-cancer patients were randomly recruited from 640 cancer hospital medical records at a Tertiary A-level hospital in Shandong province. Eventually, 164 (87.23%) sample patients were included in the statistical analysis after the non-responsive cases (4.79%) and missing value (7.98%) were removed. SDM was measured through SDM-Q-9, and the patient\'s siblings were used as indicators of Confucian Familism. Of the 164 patients, the mean SDM score was 38/100; 47.6% were thoroughly unfamiliar with their treatment plans and fell outside the decision-making procedure. Each patient had four siblings on average. Ceteris paribus, more siblings led to lower SDM. Moreover, being 56-65 years old and open-minded were associated with higher SDM, while higher satisfaction of the quality of EOL care yielded lower SDM. In conclusion, Confucian familism weakened patient-clinician SDM in EOL care for advanced cancer patients.

The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores.
Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 \"candidate cancer\" genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a \"matched therapy\" and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES).
Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68-75%). Only 94/550 patients (17%, 95%CI 14-21) received an \"AGA-matched therapy\" on progression. The most frequent AGAs leading to \"matched therapy\" included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such \"matched therapy\" improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of \"matched therapy\" was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with \"matched therapy,\" and 6-month overall survival (OS) was 62% (95%CI 52-73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/aCGH.
Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a \"matched therapy\" in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results.
ID-RCB identifier: 2014-A00966-41; ClinicalTrials.gov identifier: NCT02342158 .

Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%-30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p < .03) but not in head and neck specific symptom severity (1.2 vs 1.1, p < .60) nor in symptom interference (2.1 vs 1.7, p < .22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus.Clinical trial information. NCT01952847, and date of registration is September 30, 2013.

BACKGROUND: In end-of-life patients with advanced cancers, oral examination, oral care, and oral re-examination are crucial. Although oral symptoms are among the major complaints of end-of-life patients, few studies have focused on oral care in these patients. In this study, the association between oral symptoms and oral dryness among end-of-life patients was examined, and improvement of oral conditions after oral care interventions by a professional dentist was quantified.
METHODS: This prospective intervention study included 27 terminally ill patients with advanced cancers in a hospice ward. Professional oral care was administered every morning, and the improvement of oral conditions was assessed by comparing oral conditions before and after the intervention. Oral assessment was performed using the Oral Health Assessment Tool (OHAT) and Oral Assessment Guide. Oral dryness was evaluated through Clinical Diagnosis Classification of oral dryness and an oral moisture device. Oral cleanliness was evaluated using a bacterial counter, and tongue smears were collected for Candida examination; furthermore, oral function was recorded.
RESULTS: The presence of oral mucositis was closely associated with severe oral dryness (odds ratio [OR] = 14.93; 95% confidence interval [CI]: 1.95-114.38). The level of oral debris retention was significantly related to the degree of oral dryness (OR = 15.97; 95% CI: 2.06-123.72). The group with higher scores (OHAT > 8), which represent poor oral conditions, showed severe oral dryness (OR = 17.97; 95% CI: 1.45-223.46). Total OHAT scores (median: 7 vs 2) and those of other subgroups (lip, tongue, gums and tissues, saliva, and oral cleanliness showed a significant decrease after the intervention. Furthermore, the occurrence of mucositis (47.1% vs 0%), candidiasis rate (68.8% vs 43.8%), oral dryness self-sensation (63.6% vs 9.1%), and severe oral debris (52.9% vs 11.8%) decreased significantly.
CONCLUSIONS: Proper oral care can improve oral health and hygiene, reduce the rate of mucositis, reduce the sensation of oral dryness, increase oral moisture, and reduce the chances of oral infections among end-of-life patients. Daily oral care is necessary and can alleviate oral discomfort, increase food intake, and increase the chances of communication between end-of-life patients and their families.

OBJECTIVE: Although duodenal cancer is rare, no epidemiological research on this disease has been conducted in Asian countries. We aimed to elucidate the incidence and clinical features of duodenal cancer in Japan using a large-scale national database.
METHODS: Data of patients with primary duodenal cancer diagnosed from January 1, 2016, to December 31, 2016, were extracted from the Japanese national cancer registry. Excluding malignant neoplasm of the Vater\'s ampulla, we calculated the incidence among the population as a crude number of patients with duodenal cancer divided by the total Japanese population in 2016. We performed multivariate analyses using logistic regression models to identify risk factors for advanced cancer, defined as metastatic cancer or local invasion to adjacent organs.
RESULTS: Data on 3005 patients were included. The incidence of duodenal cancer was 23.7 per 1 000 000 person-years. In total, 56.4% of cases were detected at the localized stage. In the localized cancer group, endoscopic resection was more frequently performed (48.0%), whereas in the advanced cancer group, surgery and chemotherapy were the major treatment options (39.3% and 41.5%, respectively). Multivariate analyses identified age ≥80 years (odds ratio [OR], 1.489; 95% confidence interval [CI], 1.113-1.992; P = 0.007), incidental detection (OR, 2.325; CI, 1.623-3.331; P < 0.0001), and precise examination for symptomatic patients (OR, 10.561; CI, 7.416-15.042; P < 0.0001) as independent risk factors for advanced cancer.
CONCLUSIONS: Our study revealed the incidence of duodenal cancer in Japan. However, localized cancer was the major tumor stage at detection, resulting in a high rate of endoscopic resection.

There is uncertainty whether older patients derive a similar benefit from immune checkpoint inhibitors (ICI) as younger patients. We performed a meta-analysis of ICI trials in advanced cancers to better estimate treatment benefit in the older population.
We performed an electronic search for randomized trials of ICI, either as monotherapy or in combination with other agents. Hazard ratios (HR) for subgroups defined by different age cut-offs were extracted. Pooled overall survival (OS) treatment estimates were calculated using the inverse variance weighted method.
In nineteen trials comparing ICI monotherapy versus non-ICI treatment, there was no significant treatment-age interaction (age ≥ 65 years: N = 6064, HR 0.73; age < 65 years: N = 7250, HR 0.79; P-interaction = 0.27). Findings were similar at older age cut-offs of 70 years (age ≥ 70 years: N = 433, HR = 0.93; age < 70 years: N = 169, HR = 0.95; P-interaction = 0.91) and 75 years (age ≥ 75 years: N = 139, HR = 0.75; age < 75 years: N = 1133, HR = 0.61; P-interaction = 0.72) respectively, and for trials of ICI combination therapy.
ICI therapy improves OS in both younger and older patients with advanced cancers, and the magnitude of improvement does not depend on age. Patient selection for ICI therapy should be done based on performance status and adequate organ function independently of age.

BACKGROUND: Adhesions and infiltration into adjacent tissues are present in about 12% of gastrointestinal (GIT) cancers. These adhesions have high potential risk of malignancy. Free resection margin is a predictor of good survival in such patients. This study aims at evaluating the post-operative outcomes after multi-visceral resection of locally advanced gastrointestinal cancers.
METHODS: Ninety patients who underwent extended and multi-visceral resection for GIT cancers invading or adhering to adjacent organs have been included.
RESULTS: For gastric cancer, distal gastrectomy was performed for 12% of the cases and total gastrectomy in 20%. For recto-sigmoid cancer, anterior resection was performed in 18% and abdomino-perineal resection in 7%. Partial colectomy was performed for colonic cancer in 43% of the cases. One organ was excised with GIT tumor in 60 cases (67%). The other 30 cases (33%) required excision of more than one organ. Pathological invasion of adjacent organs was confirmed in 42% of cases. Free margins were obtained in 87% of patients. Morbidity rate was 51%. The most frequent complications were wound infection (17%), anastomotic leak (10%), and chest infection (10%). In this study, 19% required surgical re-intervention. Positive margin and positive lymph nodes (LNs) as well as mucoid adenocarcinoma were associated with a higher recurrence rate.
CONCLUSIONS: Achieving free resection margins could be a safe and feasible procedure and may offer good prognosis when followed by adjuvant therapy for patients with locally advanced GIT cancer if patients were precisely selected to have procedure done in a high volume center.