Cancer Aging Research Group (CARG) score in older adults undergoing curative intent chemotherapy: a prospective cohort study.

IMPORTANCE: The Cancer Aging Research Group (CARG) toxicity score is used to assess toxicity risk in geriatric patients receiving chemotherapy. OBJECTIVE: The primary aim was to validate the CARG score in geriatric patients treated with curative intent chemotherapy in predicting grade 3-5 toxicities. DESIGN: This was a longitudinal prospective observational study. SETTING: Tata Memorial Hospital, Mumbai, India, a tertiary cancer care referral centre. PARTICIPANTS: Patients, aged ≥65 years, with gastrointestinal, breast or gynaecological stage I-III cancers being planned for curative intent chemotherapy. A total of 270 patients were required for accrual in the study. EXPOSURES: Total risk score ranged from 0 (lowest toxicity risk) to 19 (highest toxicity risk). MAIN OUTCOMES AND MEASURES: The primary endpoint of the study was to evaluate whether the CARG risk score predicted for grade 3-5 toxicities. RESULTS: The study cohort of 270 patients had a mean age of 69 (65-83) years, with the most common cancers being gastrointestinal (79%). Fifty-two per cent of patients had atleast one grade 3-5 toxicity. The risk of toxicity was increased with an increasing risk score (42% low risk, 51% medium risk and 79% high risk; p<0.001). There was no association between either Eastern Cooperative Oncology Group (ECOG) performance status (p=0.69) or age-adjusted Charlson Comorbidity Index (p=0.79) risk categories and grade 3-5 chemotherapy toxicities. CONCLUSIONS AND RELEVANCE: This study validates the CARG risk score in predicting for grade 3-5 toxicities in geriatric oncology patients receiving curative intent chemotherapy and can be considered as the standard of care before planning chemotherapy in every elderly patient. TRIAL REGISTRATION NUMBER: CTRI/2016/10/007357; Results.

Clinico-pathological correlates and survival outcomes in 214 resected ampullary adenocarcinomas - are outcomes different in intestinal and pancreatobiliary subtypes with adjuvant gemcitabine?

BACKGROUND: Evidence suggests that intestinal type (IT) and pancreatobiliary (PB) subtypes of ampullary adenocarcinoma (AC) may have different outcomes. The current study evaluated differences in outcomes between these subtypes and the benefit of adjuvant chemotherapy (AT). METHODS: A prospectively maintained database of patients who underwent upfront resection for AC from January 2012 to March 2016 was conducted. A dedicated pathologist reported differentiation between IT and PB subtypes. RESULTS: 214 patients were included for analysis: 105 PB subtype and 109 IT subtype. With a median follow up of 46.3 months, estimated 4 year overall survival (OS) was 65.8%. In patients with stage II-III disease, lymph-node ratio (LNR) < 0.2 [Not reached (NR) vs. 30.72 months; p = 0.002], absence of perineural invasion (PNI) (NR vs. 31.61 months; p = 0.032) and AT (gemcitabine - 96.1%) (NR vs. 22.28 months) were prognostic for superior OS. There was no difference in OS between IT and PB subtypes, but both subtypes with stage II-III disease benefitted from AT statistically as compared to observation (IT: NR vs. 28.62 months; PB: 18.46 months vs. 58.09 months; p < 0.001). CONCLUSIONS: AC-IT and AC-PB did not have a different OS when treated with resection and adjuvant gemcitabine, though adjuvant therapy benefitted both subtypes individually.

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Gemcitabine-cisplatin (GC) as adjuvant chemotherapy in resected stage II and stage III gallbladder cancers (GBC): a potential way forward.

Data on adjuvant chemotherapy with gemcitabine-cisplatin (GC) in resected gallbladder cancers (GBC) are scarce. Patients who underwent upfront curative resection for GBC from 2010 to 2016 were analyzed. Patients with stage II-III GBC treated with adjuvant GC were analyzed. A total of 242 patients were evaluated, of whom 125 patients received GC regimen as adjuvant chemotherapy. The median age was 50 years (range 31-74), majority were female (77.6%), and 37 patients (29.6%) had raised CA 19.9 levels at baseline. One hundred and thirteen patients (90.4%) underwent radical cholecystectomy with R0 resections. Median number of GC administered was 6, with completion rates of 84%. Toxicity data were comprehensively available for 110 patients, with common grade 3 and grade 4 being neutropenia (9.9%), fatigue (7.3%) and febrile neutropenia (3.6%), respectively. With a median follow-up of 36.88 months, 3-year RFS was 60.3%. Patients with stage II (28%; n = 35), stage IIIA (28%; n = 35) and stage IIIB GBC (44%; n = 55) had a 3-year OS of 91.9, 67 and 58.1% (p = 0.001), respectively. Patients with stage II-III GBC undergoing R0 resections receiving adjuvant GC have good tolerance, high completion rates and encouraging outcomes in a non-trial high GBC prevalence scenario.

Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib.

BACKGROUND: The exon 11 KIT mutant gastrointestinal stromal tumors (GIST) is a heterogeneous cohort with variable biological behavior based on different mutational subtypes. METHODS: Patients with histologically proven GIST with KIT exon 11 mutations were selected from a prospectively maintained database, and evaluated for clinical characteristics and event free survival (EFS). Patients were divided into mutations upstream to codon 557 (G1), mutations involving codon 557-558 (G2) and mutation downstream to codon 558 (G3). RESULTS: A total of 90 patients satisfied the inclusion criteria for study. Substitutions, indels and duplications were seen in 23 patients. Deletions were seen in 67 patients, of which 44 patients had large deletions (>6 base pairs), while 23 has small deletions (<6 base pairs). Complex mutations were seen in 15 patients. G2 mutations were noted in 33 patients, while G1 and G3 mutations were seen 32 and 25 patients respectively. With a median follow-up of 26 months, estimated median EFS for the entire cohort was 55 months. The G2 cohort had an inferior EFS compared to the G1 and G3 cohorts (46 vs. 55 months), but this did not achieve statistical significance (univariate analysis: P=0.075). On multivariate analysis, patients undergoing radical intent surgery vs. no surgery (58 vs. 55 months; P=0.005) and G1 or G3 vs. G2 cohort (P=0.058) showed trend towards improved EFS. CONCLUSIONS: In patients with GIST exon 11 codon 557-558 mutation subset there is a trend towards an inferior survival even when treated with imatinib mesylate (IM).