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 openlabel, 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/m 2 ) (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/m 2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT. Cancer 2019;125:3184-3197.

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).

ImportanceThe Cancer Aging Research Group (CARG) toxicity score is used to assess toxicity risk in geriatric patients receiving chemotherapy.ObjectiveThe primary aim was to validate the CARG score in geriatric patients treated with curative intent chemotherapy in predicting grade 3–5 toxicities.DesignThis was a longitudinal prospective observational study.SettingTata Memorial Hospital, Mumbai, India, a tertiary cancer care referral centre.ParticipantsPatients, 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.Exposure(s)Total risk score ranged from 0 (lowest toxicity risk) to 19 (highest toxicity risk).Main outcome(s) and measure(s)The primary endpoint of the study was to evaluate whether the CARG risk score predicted for grade 3–5 toxicities.ResultsThe 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 relevanceThis 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 numberCTRI/2016/10/007357; Results.

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.

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Reactive oxygen species have been implicated in the etiology of multiorgan dysfunction syndrome and infectious complications in trauma patients by either direct cellular toxicity and/or the activation of intracellular signaling pathways. Studies have shown that the antioxidant defenses of the body are decreased in trauma patients; these include glutathione, for which N-acetylcysteine is a precursor, and selenium, which is a cofactor for glutathione. Eighteen trauma patients were prospectively randomized to a control or antioxidant group where they received N-acetylcysteine, selenium, and vitamins C and E for 7 days. As compared with the controls, the antioxidant group showed fewer infectious complications (8 versus 18) and fewer organs dysfunctioning (0 versus 9). There were no deaths in either group. We conclude that these preliminary data may support a role for the use of this antioxidant mixture to decrease the incidence of multiorgan dysfunction syndrome and infectious complications in the severely injured patient. This remains to be confirmed in larger trials.

Experimentally the dependence of E. histolytica on living bacteria in the intestine is well illustrated by the inability of E. histolytica to survive and invade the bowel wall of germ-free guinea-pigs (Phillips, Wolfe, Rees, Gordon, Wright, and Reyniers, 1955) and clinically by the observation that certain antibiotics halt acute amoebic dysentery by inhibiting the growth of intestinal bacteria (Elsdon-Dew, Armstrong, and Wilmot, 1952) but do not affect amoebic liver abscess .The mean size of E. histolytica cultured from bacteria-free human amoebic liver abscess varies according to the bacterial parasites provided (Freedman and Elsdon-Dew, 1958). However, the role of bacteria in the pathogenicity of E. histolytica is obscure; bacteria probably attack the tissues of the host and reduce the resistance or supply essential factors for the growth of amoebae. In the literature, evidence is provided to show that bacteria are necessary for the growth of amoebae in the colon, yet there are no studies to the best of our knowledge to show whether or not any specific bacteria are associated with the growth of amoebae in the intestine. MATERIAL AND METHODSIn the study of the incidence of bacteria and parasites in 800 cases of dysenteric and non-dysenteric diarrhoea, different types of amoebae were detected on microscopic stool examination in 235 patients (Antia, Chaphekar, Chhabra, Swami, and Borkar, 1961). In 203 of these patients harbouring amoebae, stool was collected for bacterial culture during sigmoidoscopic examination.BACTERIAL STUDIES The material from the colon collected with a spoon through a sigmoidoscope was transferred into nutrient broth and alkaline peptone water. Warm plates of salmonella and shigella agar, desoxycholate citrate agar, and MacConkey agar were kept ready in the incubator at 37°C. Primary plating from broth and peptone water was done immediately on all three plates.After aerobic incubation for 24 hours at 37°C., the plates were observed carefully for pale colonies. At least three such colonies were selected and each was transferred to triple-sugar-iron agar. After 18 to 24 hours' incubation, the results of triple-sugar-iron slopes tentatively identified different organisms and were confirmed with appropriate biochemical and/or agglutination tests.In some cases the plate culture showed greatly altered normal flora with a pure growth of a single organism. In such cases pink, pinkish white, pale grey, green, pale green mucoid or pale-spreading colonies were transferred on appropriate media, including triple-sugar-iron and the organisms identified with biochemical and/or agglutination tests. RESULTS

e18525 Background: There is limited data available in the literature regarding incidence and treatment of second malignancy post-chemo-radiation (CTRT) in head and neck cancer patients. Hence we planned this analysis to address this lacuna in the current literature. Methods: We have already published a randomized study of 536 head and neck cancer patients, comparing radical CTRT with weekly cisplatin with or without nimotuzumab. The database of this study was used for the current analysis. Data regarding occurrence, site, stage, treatment details and outcomes were extracted from the database. Continuous variables were expressed in terms of the median with range, while non-continuous variables were reported in percentage. Kaplan Meier method was used for estimating the overall survival (OS). Results: Out of 536 patients, 18 (3.35%) patients developed second malignancy. The most common site was head and neck (44.44%) followed by lung (27.77%), prostate, ovary, breast, gallbladder and thyroid. 16/18 (88.88%) patients developed metachronous, while 2/18 (11.11%) had synchronous second malignancy. Most of the patients (55.55%) presented with locally advanced and metastatic disease, while 44.44% of patients had early-stage disease. 8/18 (44.44%) patients received palliative treatment. Of these, 6/18 (33.33%) patients received best supportive care and 2/18 (11.11%) patients were given palliative chemotherapy and palliative radiotherapy. 10/18 (55.55%) patients received radical treatment in the form of radical surgery (22.22%), CTRT (11.11%) and radical radiotherapy (5.55%), while 16.66% patients were kept under observation only. The median OS after the diagnosis of second malignancy was 451 days (95% CI, 301.45-600.59). It was seen that median OS the diagnosis of second malignancy in the aerodigestive and non-aerodigestive system was 446 days (95% CI, 39.10 - 852.89) and 840 days (95% CI, 278.46 - 1401.53), log-rank test P-value = 0.24. Conclusions: Second malignancy is not an uncommon phenomenon in head and neck cancer patients after CTRT and if properly taken care of, the improved outcome can be expected.