The impact of computed tomography-defined sarcopenia on outcomes in head and neck cancer has been well described. Sarcopenic obesity (SO) (depleted muscle mass combined with obesity) may pose a more serious risk than either condition alone. We investigated SO and its impact on survival and critical weight loss (≥ 5 %) in patients with head and neck cancer who received curative radiotherapy (± other modalities). Retrospective analysis of computed tomography cross-sectional muscle at cervical (C3), thoracic (T2) and lumbar (L3) regions was conducted. Patients were grouped by BMI and sarcopenia status based on established thresholds. A total of 413 patients were included for analysis, the majority having oropharyngeal carcinoma (52 %), and 56 % received primary concurrent chemoradiotherapy. The majority of the cohort (65 %) was overweight or obese (BMI ≥ 25 kg/m2). Sarcopenia was found in 43 %, with 65 % having SO (n 116), equating to 28 % of the whole cohort. Critical weight loss was experienced by 58 % (n 238). A significantly higher proportion of patients with SO experienced critical weight loss (n 70 v. 19, P < 0·001) and were four times more likely to do so during treatment (OR 4·1; 95 % CI 1·5, 7·1; P = 0·002). SO was not found to impact on overall or cancer-specific survival; however, in patients with sarcopenia, those with SO had better overall survival (median 9·1 v. 7·0 years; 95 % CI 5·2, 16·8; P = 0·021). SO at the time of presentation in patients with head and neck cancer is predictive of critical weight loss during treatment, and muscle evaluation can be useful in identifying patients at nutritional risk regardless of BMI and obvious signs of wasting.

Neoadjuvant radiotherapy (RT) is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitising rectal tumours to RT to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer.

Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.

Malnutrition and sarcopenia are prevalent in patients with head and neck squamous cell carcinoma (HNSCC). Pre-treatment sarcopenia and adverse oncological outcomes in this population are well described. The impact of myosteatosis and post-treatment sarcopenia is less well known. Patients with HNSCC (n = 125) undergoing chemoradiotherapy, radiotherapy alone and/or surgery were assessed for sarcopenia and myosteatosis, using cross-sectional computed tomography (CT) imaging at the third lumbar (L3) vertebra, at baseline and 3 months post-treatment. Outcomes were overall survival (OS) at 12 months and 5 years post-treatment. One hundred and one participants had a CT scan evaluable at one or two time points, of which sixty-seven (66 %) participants were sarcopenic on at least one time point. Reduced muscle attenuation affected 93 % (n = 92) pre-treatment compared with 97 % (n = 90) post-treatment. Five-year OS favoured those without post-treatment sarcopenia (hazard ratio, HR 0·37, 95 % CI 0·16, 0·88, P = 0·06) and those without both post-treatment myosteatosis and sarcopenia (HR 0·33, 95 % CI 0·13, 0·83, P = 0·06). Overall, rates of myosteatosis were high at both pre- and post-treatment time points. Post-treatment sarcopenia was associated with worse 5-year OS, as was post-treatment sarcopenia in those who had myosteatosis. Post-treatment sarcopenia should be evaluated as an independent risk factor for decreased long-term survival post-treatment containing radiotherapy (RT) for HNSCC.

In recent years, the controlling nutritional status (CONUT) score has increasingly became an effective indicator associated with tumor prognosis. This study was conducted to synthesise data on the prognostic value of CONUT score on patients with upper tract urothelial carcinoma (UTUC) or renal cell carcinoma (RCC) undergoing nephrectomy. We designed and performed a systematic analysis of studies that verified the correlation between preoperative CONUT score and prognosis for UTUC and RCC using PubMed, Web of Science and Embase. The conclusion was clarified by pooled hazard ratios (HR) and 95% confidence intervals (95% CI). Subgroup analysis were further conducted in accordance with different primary tumor. Six studies involving 3529 patients were included in this evidence synthesis, which revealed that the CONUT score had a potential role to predict the survival of UTUC and RCC patients accepting surgery. Pooled analysis showed that the overall survival (OS, HR 2·32, p < 0·0001), cancer-specific survival (CSS, HR 2·68, p < 0·0001) and disease-free survival (DFS, HR 1·62, p < 0·00001) were inferior in the high CONUT score group when compared with low score group. Subgroup analysis revealed that this result was in line with UTUC (OS: HR 1·86, p = 0·02; CSS: HR 2·24, p = 0·01; DFS: HR 1·54, p < 0·00001) and RCC (OS: HR 3·05, p < 0·00001; CSS: HR 3·47, p < 0·00001; DFS: HR 2·21, p = 0·0005) patients respectively. Consequently, the CONUT score is a valuable preoperative index to predict the survival of patients with UTUC or RCC undergoing nephrectomy.

Sarcopenia, defined as decrease in skeletal muscle mass (SMM) and strength, might be associated with reduced survival. We investigated the impact of sarcopenia and decrease in SMM in patients with advanced pancreatic cancer during FOLFIRINOX (FX) therapy. Consecutive sixty-nine patients who received FX were evaluated. Skeletal muscle index (SMI) (cm2/m2) was used to evaluate SMM. The cut-off value of sarcopenia was defined as SMI <42 for males and <38 for females, based on the Asian Working Group for sarcopenia criteria. Sarcopenia was diagnosed in thirty-three (48 %) subjects. Comparison of baseline characteristics of the two groups (sarcopenia group: non-sarcopenia group) showed a significant difference in sex, tumour size and BMI. There was no significant difference in the incidence of adverse events with grades 3–5 and progression-free survival (PFS) during FX between the two groups (PFS 8·1 and 8·8 months; P = 0·88). On the multivariate analysis, progressive disease at the first follow-up computed tomography (hazard ratio (HR) 3·87, 95 % CI 1·53, 9·67), decreased SMI ≥ 7·9 % in 2 months (HR 4·02, 95 % CI 1·87, 8·97) and carcinoembryonic antigen ≥ 4·6 (HR 2·52, 95 % CI 1·10, 6·11) were significant risk factors associated with poor overall survival (OS), but sarcopenia at diagnosis was not. OS in patients with decreased SMI of ≥7·9 % and <7·9 % were 10·9 and 21·0 months (P < 0·01), respectively. In conclusion, decrease in SMM within 2 months after the initiation of chemotherapy had significantly shorter OS, although sarcopenia at diagnosis did not affect OS. Therefore, it might be important to maintain SMM during chemotherapy for a better prognosis.

Preoperative nutritional status plays an important role in predicting postoperative outcomes. Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) are good tools to assess patients’ nutritional status. They have been used in predicting outcomes in various malignancies, but few studies have focused on pancreatic adenocarcinoma (PDAC) patients. Totally, 306 PDAC patients were enrolled. The propensity score matching (PSM) method was introduced to eliminate the baseline inequivalence. Patients with different PNI (or CONUT) scores showed inequivalence baseline characteristics, and patients with compromised nutritional status were related with a more advanced tumour stage. After PSM, the baseline characteristics were well balanced. Both low PNI (≤45) and high CONUT (≥3) were independent risk factors for poor overall survival (P < 0·05), and the result remained the same after PSM. Survival analysis demonstrated both patients with low PNI and high CONUT score were associated with poorer survival, and the result remained the same after PSM. The results of AUC indicated that CONUT might have a higher sensitivity and specificity in predicting complications and survival. Preoperative low PNI (≤45) and high CONUT (≥3) scores might be reliable predictors of prognosis and surgical complications in PDAC patients. Compared with PNI, CONUT might be more effective.

Health technology assessment (HTA) recommendations informed by patient concerns are seen to ensure democracy and legitimacy. We explored how written and oral patient involvement in two HTAs was reported on in publicly available final recommendations and discussion summaries of appraisal committees from three HTA bodies. We aimed to gain insights into how patient input was utilized by appraisal committees to better understand the goals of patient involvement and how these are being achieved. In each of the three HTA bodies, templated submission questionnaires provide a formal process for seeking written patient group input. Additionally, the National Institute for Health and Care Excellence (NICE) selects patient experts to provide a templated submission and attend appraisal committee meetings. For Scottish Medicines Consortium (SMC), a patient advocate and clinician combined meeting (PACE) discussed the cancer drug, referred to in the final recommendation. The discussion summaries of all appraisal committees contained references to patient involvement. Where two mechanisms for patient involvement were provided, oral input from the expert patients and PACE were more clearly documented than information from written patient group submissions. NICE reports focused on the perspective of the patient expert. The SMC report highlighted feedback from the PACE throughout. We suggest that the lack of clear reporting on the use of patient group input in deliberations and therefore accountability to patient groups limits progress in patient involvement in HTA. Patient groups may therefore not have a clear understanding of what information they can best provide to inform deliberations, and in reporting back to members.

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

The aim of this retrospective study was to investigate the prognostic significance of pre-treatment immunological and nutritional statuses in patients with locally advanced gastric cancer (GC), and to use the risk factors to develop a predictive score. A total of 731 patients who underwent gastrectomy for stage II/III GC from November 2010 to December 2015 were recruited into this retrospective study. On the basis of univariate and further multivariate Cox regression analyses, decreased pretreatment lymphocyte count (<1·5×109/litre) and prealbumin concentrations (<180 mg/l) were identified to be independently associated with poorer overall survival (OS) and disease-free survival (DFS). Low albumin concentrations (<33 g/l) were identified as an independent risk factor only for OS, but not for DFS. Thereafter, patients who had a decreased prealbumin concentration and lymphocyte count were given a combination of serum prealbumin concentration and lymphocyte count (Co-PaL) score of 2. Patients with only one or neither of these concentrations were given a Co-PaL score of 1 or 0, respectively. Both the OS and the DFS time were inversely related to the Co-PaL scores, and the differences among the three groups were all significant. In contrast, the prognosis did not differ significantly between patients with good nutrition and those with mild to moderate malnutrition according to the prognostic nutritional index. This study indicated that the simple scoring system could accurately predict the prognosis of patients who underwent gastrectomy for stage II/III GC. The score might be helpful in terms of clinical preoperative decision-making.

Objectives: In clinical trials of new cancer drugs, reliable data for progression-free survival will often become available far sooner than reliable data for overall survival. The aim of this study was to determine how many months it would be expected that any given new drug for metastatic breast or colorectal cancer will add to overall survival times given that the number of months the drug adds to progression-free survival times relative to a standard drug is roughly already known.

Methods: A literature search was conducted over Medline for randomized controlled trials (RCTs) published between January 1980 and August 2008 that assessed the effect of a drug treatment in comparison to an alternative drug treatment on patients with either metastatic breast or metastatic colorectal cancer.

Results: The literature search found 95 and 74 RCTs for metastatic breast and colorectal cancer, respectively, that satisfied the study's inclusion criteria. The results from these trials are consistent, in the case of each of these two metastatic cancers, with gains in time to disease progression being generally associated with no gains or with very slight gains or losses in post-progression survival (i.e., the time between disease progression and death).

Conclusions: It would appear that drugs for metastatic breast or colorectal cancer that extend, by a given amount, the time period between the start of treatment and disease progression (i.e., time to progression) have a strong tendency to extend, by roughly the same amount, the period between the start of treatment and death (i.e., overall survival).

Objectives: Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint.

Methods: A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROS from observed HRPFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption.

Results: Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HRPFS was a statistically significant predictor of HROS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROS agreed with observed HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses.

Conclusions: This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.