North Central Cancer Treatment Group

O câncer de pulmão é o tipo de câncer que mais mata em todo o mundo, acometendo anualmente milhões de pessoas. É classificado em câncer de pulmão de células não pequenas (NSCLC) e câncer de pulmão de células pequenas (SCLC), sendo o NSCLC o tipo mais comum, representando 85% dos casos. Seus sintomas são muito variados, visto que se dá devido aos efeitos locais do tumor e os tratamentos atuais ainda são pouco eficientes nos estágios mais avançados. Fatores genéticos e ambientais adversos podem favorecer a gênese do câncer de pulmão, ainda que o principal fator de risco continue sendo o tabagismo. Com o objetivo de discutir o potencial carcinogênico da fumaça da Cannabis (maconha) em comparação com a do tabaco, foi realizada uma revisão bibliográfica analisando os constituintes químicos da fumaça do cigarro de tabaco e de maconha buscando antever se a mesma apresenta risco semelhante ao da fumaça do tabaco na gênese desta patologia. No cigarro de tabaco são encontradas diversas substâncias que possuem potencial carcinogênico sendo a nitrosamina cetônica derivada da nicotina (NNK) e vários hidrocarbonetos policíclicos aromáticos (PAH) tidos como os principais. O cigarro de maconha é consumido de forma muito semelhante ao cigarro de tabaco, fazendo com que o usuário também seja exposto a substâncias tóxicas provenientes da queima da maconha. Na fumaça da maconha o NNK está ausente, porém contêm PAHs juntamente com outras substâncias com ações potencialmente carcinogênicas. Algumas pesquisas envolvendo estudos de casos conectam o uso da maconha com o câncer de pulmão. Contudo, estudos específicos relacionando diretamente os componentes da fumaça da maconha com o câncer de pulmão, sob nosso ponto de vista, são ainda insuficientes. Embora muitas substâncias tóxicas e/ou carcinogênicas estejam presentes na fumaça da maconha em concentrações semelhantes às do cigarro comum, não encontramos dados suficientes na literatura consultada que permitam concluir que o uso da maconha possua o mesmo potencial carcinogênico do cigarro do tabaco. Palavras-chave: Tabagismo. Maconha. Nicotina. Canabinoides. Carcinoma

Abstract The authors have withdrawn this preprint due to author disagreement.

Abstract BACKGROUND NRG-CC001 sought to evaluate the neuro-protective effects of avoiding the peri-hippocampal stem cell niche using intensity-modulated radiotherapy during WBRT. METHODS Patients with brain metastasis were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+ Memantine (M) (30Gy in 10 fractions). Standardized NCF tests and the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) were obtained at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure defined using the reliable change index. Pre-specified secondary endpoints included patient-reported symptoms using the MDASI-BT. Time to NCF was reported as cumulative incidence (with death without NCF failure as a competing risk); between-arms differences were tested using Gray’s test. Deterioration at discrete time-points were tested using chi-square tests. MDASI-BT symptom burden, interference, and cognitive and neurologic burden were analyzed using mixed effects models and t-tests within the model using Hochberg’s multiplicity adjustment. RESULTS A total of 518 patients were randomized from 7/2016 to 3/2018. Median follow-up for alive patients was 12.1 mos, with no difference between arms in terms of toxicity, overall survival or intracranial progression-free survival. HA-WBRT+M was associated with lower risk of NCF failure (adjusted HR=0.739, 95% CI: 0.577–0.945, p=0.0.016), with differences first noted at 4 mos in Trail Making Test Part-B (23.3% vs. 40.4% deteriorated, p=0.012). Age did not dilute treatment effect. HA-WBRT+M was associated with reduced cognitive symptom burden in an imputed model (estimate=-0.29, p=0.0425), and also reduced overall symptom burden (p< 0.0001) and interference (p< 0.0016) at 6 mos. CONCLUSIONS The addition of HA to WBRT+M preserved NCF and reduced patient reported cognitive symptom burden, overall symptom burden and symptom interference and should be considered standard of care for any patient fit enough to have WBRT. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.

To investigate and compare the effects of breast-conserving therapy (BCT) and mastectomy on the disease recurrence and long-term survival in early-stage luminal breast cancer and the difference in prognosis across diverse luminal subtypes receiving single surgical modality. The databases of PubMed and Embase were retrieved to select eligible trials that were published from inception to 13 November 2018. The clinical trials that offered the details about recurrent disease and/or survival in luminal tumors underwent BCT or mastectomy met the inclusion criteria (n=24). With the random- or fixed-effect model basing on heterogeneity Chi test with its significant level of P < .1, pooled odds ratio (OR) with its 95% CI, and P value were identified for endpoints. The analyzed data were constituted of 25 qualified trials with 13,032 unique women suffered from luminal cancers. The fixed-effect models were utilized. On the LRR regarding BCT versus mastectomy, the pooled data indicated no significant difference in luminal carcinomas (OR, 0.84; 95%CI, 0.43-1.64; P = .61; n = 867). In BCT cohort, the pooled data showed that there were some significant benefits favoring luminal A over luminal B in LR (OR, 0.61; 95%CI, 0.46-0.81; P = .0007; n = 5406), DM (OR, 0.53; 95%CI, 0.41-0.69; P < .00001; n = 4662), DFS (OR, 0.59; 95%CI, 0.36-0.96; P = .03; n = 776) and OS (OR, 0.65; 95%CI, 0.42-0.99; P = .05; n = 1149), but not in LRR (OR, 0.74; 95%CI, 0.48-1.13; P = .16; n = 3732), coupled with luminal A/B over luminal-HER2 in LRR (OR, 0.43; 95%CI, 0.25-0.76; P = .004; n = 890), DM (OR, 0.56; 95%CI, 0.35-0.90; P = .02; n = 1396), DFS (OR, 0.47; 95%CI, 0.27-0.83; P = .009; n = 532); in mastectomy cohort, there were apparent advantages of LRR (OR, 0.58; 95%CI, 0.36-0.92; P = .02; n = 1768), LR (OR,0.56; 95%CI, 0.38-0.83; P = .004; n = 1209), DM (OR, 0.58; 95%CI, 0.40-0.84; P = .004; n = 652) and OS (OR, 0.62; 95%CI, 0.43-0.89; P = .009; n = 652) in luminal A vs luminal B. For early luminal breast cancer, the equality of LRR was achieved in BCT and mastectomy. In comparison, luminal A cancers benefit the most improved tumor re-appearence and survival in luminal diseases regardless of the option of surgical modality, whereas luminal-HER2 is affected by the worst clinical outcomes in them who follows BCT.

Infant leukaemia (IL) is extremely rare with fewer than 150 cases occurring each year in the United States. Little is known about its causes. However, recent evidence supports a role of de novo mutations in IL aetiology. Parental age has been associated with several adverse outcomes in offspring, including childhood cancers. Given the role of older parental age in de novo mutations in offspring, we carried out an analysis of parental age and IL. We evaluated the relationship between parental age and IL in a case-control study using registry data from New York, Minnesota, California, Texas, and Washington. Records from 402 cases [219 acute lymphoblastic leukaemia (ALL), 131 acute myeloid leukaemia (AML), and 52 other] and 45392 controls born during 1981-2004 were analysed. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Estimates were adjusted for infant sex, birth year category, maternal race, state, and mutually adjusted for paternal or maternal age, respectively. Infants with mothers' age ≥40years had an increased risk of developing AML (OR 4.80, 95% CI 1.80, 12.76). In contrast, paternal age <20 was associated with increased risk of ALL (OR 3.69, 95% CI 1.62, 8.41). This study demonstrates increased risk of infant ALL in relation to young paternal age. Given record linkage, there is little concern with recall or selection bias, although data are lacking on MLL gene status and other potentially important variables. Parent of origin effects, de novo mutations, and/or carcinogenic exposures may be involved in IL aetiology.

Mutations in Charcot-Marie-Tooth disease (CMT) genes are the cause of rare familial forms of polyneuropathy. Whether allelic variability in CMT genes is also associated with common forms of polyneuropathy-considered "acquired" in medical parlance-is unknown. Chemotherapy-induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable. We used CIPN as a clinical model to investigate the association of non-CMT polyneuropathy with CMT genes. A total of 269 neurologically asymptomatic cancer patients were enrolled in the clinical trial Alliance N08C1 to receive the neurotoxic drug paclitaxel, while undergoing prospective assessments for polyneuropathy. Forty-nine CMT genes were analyzed by targeted massively parallel sequencing of genomic DNA from patient blood. A total of 119 (of 269) patients were identified from the 2 ends of the polyneuropathy phenotype distribution: patients that were most and least susceptible to paclitaxel polyneuropathy. The CMT gene PRX was found to be deleteriously mutated in patients who were susceptible to CIPN but not in controls (p = 8 × 10(-3)). Genetic variation in another CMT gene, ARHGEF10, was highly significantly associated with CIPN (p = 5 × 10(-4)). Three nonsynonymous recurrent single nucleotide variants contributed to the ARHGEF10 signal: rs9657362, rs2294039, and rs17683288. Of these, rs9657362 had the strongest effect (odds ratio = 4.8, p = 4 × 10(-4)). The results reveal an association of CMT gene allelic variability with susceptibility to CIPN. The findings raise the possibility that other acquired polyneuropathies may also be codetermined by genetic etiological factors, of which some may be related to genes already known to cause the phenotypically related Mendelian disorders of CMT.

e16513 Background: Despite the fact that chronological age alone does not determine tolerance to cancer treatment, there is a general perception that elderly cancer patients do not receive standard treatment. We sought to review breast cancer patients above 80 years in our practice. Methods: Retrospective analysis was performed ofall women with breast cancer over the age of 80 either at the time of diagnosis or at the time of relapse since July 2005 till July 2011. Results: There were total of 492 breast cancer patients seen during the study period, 207 below 65, 213 between 66-79 and 70 above 80. 59 women met the study criteria. The median age was 86 (81to 99 years). 47 had activities of independent living, 8 were in an assisted living facility and 4 in nursing homes. Median Charlson Co morbidity Index was 2 (0-5). Pathological types: DCIS 2, Invasive ductal carcinoma 50, invasive lobular carcinoma 6 and 1 had apocrine carcinoma. 50 had ER+, PR+ and Her-, 2 patients had triple negative disease and 4 Her+. 2 patients had stage 0, 22 stage I, 23 Stage II, 7 stage III and 5 stage IV. All patients stage 0-III had surgical management, 39 had breast conservative surgery with sentinel node biopsy and 15 had mastectomy. Out of 28 patients referred for adjuvant radiation therapy 17 received it. 49 patients received hormone treatment (39 aromatase inhibitors- AIs and 14 tamoxifen) Chemotherapy was offered but refused by two stage III patients. 2 Her + patients received and tolerated well trastuzumab based chemotherapy. After a median follow up of 48 months (8-120 months) there was 1 local recurrence, 1 distant relapse and 14 deaths ( 11 from other causes 3 from breast cancer). Conclusions: In ourpractice, a majority of octogenarians and nonagenarians live independently and have minimal co morbidities and tolerate standard surgical and hormonal treatment. Although radiation therapy would be considered optional in this group of women, it was offered based on predicted longevity. Mortality form other causes was higher than that from breast cancer ( 18% vs 5%).