There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses.

Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy.

At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17].

Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Brain metastases (BM) are common in metastatic nonsmall cell lung cancer (NSCLC). However, routine neuroimaging in asymptomatic patients with metastatic NSCLC is controversial as there is no conclusive evidence of benefit from the detection and treatment of asymptomatic BM. Herein, we evaluated the prevalence of asymptomatic BM and its treatment implications in a resource-limited setting.

Consecutive patients with newly diagnosed, treatment-naïve, metastatic, nonsquamous NSCLC (NS-NSCLC) were included. Subjects who already had clinical or radiological features suggestive of BM were excluded from the study. All eligible subjects underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain. Management of the detected BM was at the discretion of the treating clinicians.

Among 809 subjects who were screened, 100 (12.4%) were included in the study and underwent MRI. BM was present in 30 (30%) of the subjects and absent in the remaining 70 subjects. A majority of BM were multiple (70%), involved the frontal lobe commonly (73.3%), and had a mean (standard deviation) size of 13.2 (7.3) mm. Detection of BM resulted in a treatment alteration in 17 (17%) of the study subjects (brain irradiation, n = 17, change in targeted therapy, n = 3) with BM. There was no difference in survival of patients who underwent treatment alteration for management of BM compared to those who did not ( P = 0.132).

About one-third of patients with metastatic NS-NSCLC had BM in MRI despite the absence of symptoms. Despite treatment of the majority of the patients with BM with brain irradiation, there was no demonstrable survival benefit. Hence, we conclude that although routine neuroimaging of asymptomatic patients with newly diagnosed metastatic NSCLC may result in treatment alteration (primarily brain irradiation) in a small proportion of patients, it may not influence outcomes in resource-constrained settings.

Lung cancer is an increasing problem in the developing world due to rising trends in smoking, high incidence of air pollution, lack of awareness and screening, delayed presentation, and diagnosis at the advanced stage. Even after diagnosis, there are disparities in access to health care facilities and inequitable distribution of resources and treatment options. In addition, the shortage of trained personnel and infrastructure adds to the challenges faced by patients with lung cancer in these regions. A multi-pronged effort targeting tobacco cessation, health promotion and awareness, capacity building, and value-based care are the need of the hour.

Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited.

Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin-stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1-positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated.

The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1-positive subjects were similar to PD-L1-negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS.

PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC.

Irinotecan (CPT11) is an important drug for small cell lung cancer (SCLC) chemotherapy (CTx). UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms can influence CPT11-related toxicity. This study aimed to assess prevalence of UGT1A1 polymorphisms and their association with clinical outcomes in patients with SCLC on CPT11-CTx.

An observational cohort of treatment-naïve patients with SCLC was given CPT11-platinum doublet at a referral center in North India over 3 years. Clinical outcomes assessed were hematological and gastrointestinal toxicity (Common Terminology Criteria for Adverse Events, version 3.0), response rates (RECIST), and overall survival (OS). Peripheral blood was drawn from all enrolled patients just prior to CPT11-CTx initiation, and genomic DNA was isolated. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism for UGT1A1*7, UGT1A1*6, and UGT1A1*27 and by PCR-DNA sequencing for UGT1A1*28. Patients were classified as homozygous wild-type (WT/WT), heterozygous mutant (WT/M), or homozygous mutant (M/M) for each polymorphism assessed.

Of 140 patients enrolled, no mutant alleles were found for UGT1A1*27 or UGT1A1*7. Frequency of UGT1A1*6 polymorphisms (n = 111) was 89.2% for WT/WT, 8.1% for WT/M, and 2.7% for M/M. For UGT1A1*28 (n = 102), this was 41.2% for WT/WT, 43.1% for WT/M, and 15.7% for M/M. UGT1A1*6 WT/WT patients tolerated >95% predicted CPT11 dose more frequently (59.6% vs. 25.0% in WT/M-M/M combined group; p = .026). The UGT1A1*6 WT/M-M/M group also experienced severe (grade ≥3) diarrhea (41.7% vs. 17.2% in WT/WT; p = .044) and mucositis (41.7% vs. 8.1% in WT/WT; p = .005) more frequently. On multivariate logistic regression analysis, UGT1A1*6 WT/M-M/M status was the only variable associated with occurrence of both mucositis (odds ratio [OR], 10.4) and severe diarrhea (OR, 4.8). UGT1A1*28 WT/M-M/M patients had better OS (320 days [95% confidence interval, 203-437] vs. 216 days [95% confidence interval, 140-292] in WT/WT group; p = .047). On multivariate Cox proportional hazards analysis, UGT1A1*28 WT/M-M/M status was independently associated with better OS (hazard ratio, 0.35), whereas lack of objective radiological response, moderate/heavy smoking, and increasing age were associated with worse OS.

UGT1A1*6 and UGT1A1*28 polymorphisms were associated with increased gastrointestinal toxicity and improved OS, respectively, in North Indian patients with SCLC receiving CPT11-CTx.

UGT1A1 gene polymorphisms are known to influence irinotecan-related toxicity. In this prospective cohort study of patients with small cell lung cancer receiving first-line irinotecan-platinum chemotherapy, the prevalence of UGT1A1*6 polymorphisms was found to be 10.8% UGT1A1*6 and 58.8% UGT1A1*28 homo/heterozygous mutant, respectively. UGT1A1*6 homo/heterozygous mutant status was associated with severe diarrhea and mucositis. UGT1A1*28 homo/heterozygous mutant status was independently associated with improved overall survival.

Maintenance chemotherapy (MC) with pemetrexed is a commonly used strategy in nonsquamous non-small cell lung cancer. However, most of the available evidence is from subjects with good performance status (PS), while data on the real-world utility and safety of this strategy in subjects with various categories of PS is limited. We performed a retrospective analysis of multicentric data of 3 centers from India. All patients with advanced nonsquamous non-small cell lung cancer who received MC with pemetrexed after induction chemotherapy were included. Subjects were divided into 2 groups based on baseline Eastern Cooperative Oncology Group score before initiation of induction chemotherapy as good PS (<2) and poor PS (≥2). Progression-free survival, overall survival, and toxicity were assessed in the study population. A total of 290 subjects were included in the study, of whom a significant proportion (n = 104, 35.9%) had poor PS. Survival was better in subjects with good PS as compared to those with poor PS (1-year progression-free survival: 43.5% vs 29.8%, P = 0.021; 1-year overall survival: 61.8% vs 48.1%, P = 0.023). Grade 3/4 toxicity was observed in 14.5% of subjects during MC and was not different between both groups (P = 0.287). Renal dysfunction was more common in subjects who received ≥10 cycles of MC (10.7% vs 4.2%, P = 0.040). MC with pemetrexed appeared to be beneficial and safe in the real-world setting regardless of the baseline PS. However, survival benefit was more pronounced in subjects with good PS at baseline. Renal dysfunction was more frequently encountered in subjects who received prolonged MC.

Vitamin B12 and folic acid (FA) supplementation (B12-FAS) reduces hematologic toxicity with pemetrexed-based chemotherapy (PEM). However, the basis for recommending 1 week of B12-FAS before PEM initiation has never been proven in a randomized trial.

An open-label, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) was conducted to compare hematologic toxicity between patients with locally advanced/metastatic nonsquamous non-small cell lung cancer who initiated PEM after 5 to 7 days of B12-FAS (delayed arm [DA]) versus those who received B12-FAS simultaneously (≤24 hours) with PEM initiation (immediate arm [IA]). Every 3 weeks, all enrolled patients received pemetrexed (500 mg/m2 ) AND either cisplatin (65 mg/m2 ) OR carboplatin (area under the curve = 5.0 mg/mL per minute) on day 1 for a maximum of 6 cycles. Supplementation consisted of oral FA 1000 μg daily and intramuscular vitamin B12 1000 μg every 3 weeks. The primary outcome was any grade of hematologic toxicity and secondary outcomes included grade 3/4 hematologic toxicity, the relative dose intensity delivered, and changes in serum levels of B12/FA/homocysteine.

Of 161 patients (IA, n = 81; DA, n = 80) recruited, 150 (IA, n = 77; DA, n = 73) received ≥1 cycle and were included in a modified intention-to-treat analysis. Baseline anemia prevalence was 34.7% (IA, 32.5%; DA, 37%; P = .56). The incidence of any grade anemia, leukopenia, neutropenia, and thrombocytopenia was 87% versus 87.7% (P = .90), 37.7% versus 28.8% (P = .25), 20.8% versus 15.1% (P = .36), and 31.2% versus 16.4% (P = .04), respectively, in the IA and DA, respectively. Grade 3/4 cytopenias and median relative dose intensities delivered (pemetrexed, 93.5%; platinum, 91%) were similar in both arms. After cycle 3 (compared with baseline), serum homocysteine levels were lower, whereas FA and B12 levels were higher. In the DA, serum FA and B12 levels on day 1 of cycle 1 (after 5-7 days of B12-FAS) were significantly higher than at baseline, but homocysteine levels were similar.

Simultaneous B12-FAS initiation with a pemetrexed-platinum doublet chemotherapy regimen is feasible and does not lead to enhanced hematologic toxicity. Serum homocysteine levels are unaffected by 5 to 7 days of B12-FAS.

Lung cancer (LC) chemotherapy results in several adverse events (AEs). Data regarding supportive care medications (SCMs) offered to prevent/treat AEs in resource-limited settings are lacking. A prospective observational study was carried out to find the effectiveness of SCMs in real-life setting.

Newly diagnosed LC patients receiving first-line chemotherapy at a tertiary referral center in North India (from July 2014 to September 2015) were enrolled. Incidence, timing of onset, duration, and grades of chemotherapy-related AEs were recorded. We assessed compliance to mandatory SCMs using a structured questionnaire. Patients also recorded various symptoms, frequency of need-based SCMs, visits to local practitioners, and hospitalization (if any) during the intercycle period.

Of the 112 patients enrolled, majority were males (83.9%, n = 94), current/ex-smokers (82.1%, n = 92), had advanced stage (Stage IIIB = 33.9% [n = 38] and Stage IV = 46.4% [n = 52]), and were non-small cell lung cancer (72.3%, n = 81). AEs were reported in 566 cycles (94%) out of a total of 602 chemotherapy cycles. Diarrhea was the most common AE (180 cycles, 29.9%) developing after a mean (standard deviation) duration of 3.6 (2.5) days and lasting for 4 (3.3) days. Vomiting (138 cycles, 22.9%) and constipation (121 cycles, 20.1%) were other common AEs. Grade 3/4 AEs occurred in 6.9% (39/566) cycles. Need-based SCMs were required in 479 of the 566 cycles (84.6%). Proportion of patients with Grade 3/4 AEs and hospitalization was highest for mucositis (16.1% Grade 3/4 and 9.7% hospitalized); followed by vomiting (10.1% Grade 3/4 and 8.7% hospitalized). Anemia was seen in 441 of 602 chemotherapy cycles (73.3%). Frequency and severity of anemia continued to increase with each chemotherapy cycle.

LC chemotherapy has a high prevalence of AEs. However, the majority are low grade recovering with need-based SCMs, without any need for hospitalization.

To establish the Karnofsky performance status (KPS) categories which would facilitate the interconversion of the KPS scale to the Eastern Cooperative Oncology Group (ECOG) performance status (PS) scale.

This was a retrospective analysis of all patients attending the lung cancer clinic at a tertiary care center over a 5-year period (September 2009 to August 2014). All patients were assessed with both KPS and ECOG PS scales at each visit. Correlation between KPS and ECOG PS was assessed using Spearman's correlation coefficient. KPS categories equivalent to ECOG PS scores were compared using hit rate and weighted kappa (κw).

A total of 1501 patients were assessed over the study period, providing 5844 paired KPS and ECOG PS assessments. The study cohort had a mean (standard deviation; SD) age of 58.4 (10.8) years, with the majority being current or ex-smokers (76.9%) and males (82.3%). Non-small cell lung cancer was the most common histological type (n = 1196, 79.7%) with the majority having advanced (stage IIIB/IV) disease (83.4%). Mean baseline KPS and ECOG PS scores were 77.6 (SD = 14.4) and 1.5 (SD = 1) respectively. The most frequent KPS score was 80 (29%), and the most frequent ECOG PS score was 1 (43%). The overall correlation between KPS and ECOG PS was good (Spearman r = -0.84, P < 0.0001) but ranged from -0.727 to -0.972 between visits. KPS categories derived from our cohort [10-40 (ECOG 4), 50-60 (ECOG 3), 70 (ECOG 2), 80-90 (ECOG 1), 100 (ECOG 0)] performed better [hit rate 78.1%, κw = 0.749 (0.736-0.762) P < 0.0001] than those suggested in the past literature.

The current study provides the largest set of paired KPS-ECOG assessments to date. We suggest that the KPS categories 10-40, 50-60, 70, 80-90, and 100 are equivalent to ECOG PS categories of 4, 3, 2, 1, and 0 respectively.

Symptom palliation is an important objective of treatment in advanced/metastatic lung cancer (LC). Significant psychological, minor physical symptoms and several social/emotional issues often go unnoticed. This prospective study aimed to evaluate utility of patients' perspectives [self-reported symptom assessment by revised Edmonton Symptom Assessment System (ESAS-r) and self-reported functional status by Patient-Reported Functional Status (PRFS)] amongst LC patients undergoing chemotherapy.

Consecutive newly diagnosed treatment-naïve LC patients attending a tertiary referral center in North India from January 2014 to March 2015 were included. All patients received standard histology-guided platinum-doublet chemotherapy. ESAS-r and PRFS questionnaires were administered under guidance, once at the time of initial assessment/diagnosis, repeated at start of chemotherapy, before C4, and after completion of chemotherapy (end of chemotherapy (EOCTx)). Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire was also administered. Baseline and post-treatment scores were compared.

Majority of 133 patients enrolled were males (86.5%,n = 115), were current/ex-smokers (81.2%, n = 108), had advanced stage [IIIB = 30.1% (n = 40), IV = 52.6% (n = 70)], and were of non-small-cell type (NSCLC;84.2%,n = 112). On baseline ESAS-r, the highest mean symptom scores were observed for tiredness followed by anorexia. Mean ESAS-r scores before C4 as well as at EOCTX were significantly better than baseline ESAS-r scores in all its components except nausea. Similarly, PRFS before C4 and EOCTx was significantly improved compared to baseline. However, Karnofsky Performance Scale (KPS) and Eastern Cooperative Oncology Group Performance Status assessed at baseline did not show significant improvement at treatment completion. FACT-L score at EOCTx showed significant improvement from baseline in physical and functional well-being domains but not for social/family and emotional well-being domains.

This study validated utility of ESAS-r and PRFS in Indian LC patients. These instruments should be used in routine clinical practice besides physicians' assessment of PS (KPS/ECOG).

There is a paucity of literature on symptom score (SS) plus fiberoptic bronchoscopy (FOB) -based response evaluation (RE) to chemotherapy for lung cancer. This study aimed to compare the reliability of RE by SS, chest radiograph (CXR), and FOB with computed tomography (CT) -based assessment (Response Evaluation Criteria in Solid Tumors (RECIST) and WHO criteria) for lung cancer chemotherapy.

This was a prospective observational study involving treatment-naïve patients with lung cancer planned for chemotherapy, with one or more lesions on FOB and CT. Patients underwent assessment twice by SS, CXR, FOB, and CT (at baseline and after chemotherapy). Six symptoms (dyspnea, cough, chest pain, hemoptysis, anorexia, and weight loss) were noted on visual analog scale. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from the first four and all six symptoms, respectively, as the mean of individual SS. Bronchoscopic findings were recorded as per European Respiratory Society classification for tracheobronchial stenosis. Responses were classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by each method. For FOB and SS, improvement or worsening by ≥ 20% was taken as PR or PD, respectively, whereas < 20% change was considered SD. Agreements were tested using Cohen's κ statistic.

All individual SS, RSB, and TSB scores, and the number and distribution of FOB lesions improved significantly after chemotherapy. Individually, CXR and SS had no or minimal agreement with FOB-based and CT-based responses. RECIST and WHO criteria had strong agreement overall (Cohen's κ = 0.872) and perfect agreement for PD (Cohen's κ = 1.000). Cohen's κvalues for FOB-based assessment with RECIST and WHO were 0.324 and 0.349, respectively for overall RE, and 0.462 and 0.501 for differentiating responders (CR and PR) from nonresponders (SD and PD), respectively. Cohen's κvalues for PD were 0.629 (FOB alone), 0.672 (FOB and RSB), 0.739 (FOB and TSB), and 0.764 (FOB and CXR).

CT-based assessment should remain the reference for objective RE of chemotherapy in lung cancer. A combination of FOB and CXR may be used as a surrogate to diagnose PD if CT is not feasible.

Pemetrexed is the preferred chemotherapeutic drug for nonsquamous, non-small-cell lung cancer patients whenever the predictive molecular biomarkers for targeted therapy have either not been assessed or are absent. As per manufacturers' instructions, supplementation with folic acid (FA; folate) at a dose of 350 to 1000 μg daily should be started seven days before the first dose of pemetrexed-based chemotherapy and continued during therapy and for 21 days after therapy cessation. Vitamin B12 injections (1000 μg intramuscularly) should also be started one week before the first dose of chemotherapy. However, the evidence for delaying chemotherapy by one week for the purpose of providing vitamin B12 and FA supplementation is not robust. Observational and prospective single-arm studies have not shown any increased toxicity if pemetrexed was started earlier than the recommended duration of supplementation. In a resource-constrained setting, the standard (conventional) approach would lead to one additional visit and a 1-week chemotherapy delay, both of which could be inconvenient for patients. Hence, an open-label, randomized trial (PEMVITASTART [Vitamin Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy]; ClinicalTrials.gov identifier, NCT02679443) is being undertaken to evaluate whether any differences exist in pemetrexed-related hematologic toxicity among patients who receive delayed initiation of chemotherapy (after 5-7 days of vitamin B12 and FA supplementation [delayed arm]) compared with those for whom vitamin B12 and FA supplementation is started simultaneously (within 24 hours) of chemotherapy initiation (immediate arm). The present report describes the rationale and detailed design of the PEMVITASART trial.

There are limited data from developing countries on graded baseline symptom (BS) assessment in lung cancer. This prospective study aimed to assess the prognostic role of BS and correlation of BS with comorbidity, demographic, and investigation profiles in a cohort of 238 patients with lung cancer undergoing first-line chemotherapy over a 15-month period.

The Medical Research Council (MRC) scale was used to assess dyspnea, whereas the visual analog scale (VAS; score of 1 to 10) was used to assess anorexia, fatigue, chest pain, and cough. Weight loss (WL) was noted as percentage of pre-illness baseline. All patients received histology-guided platinum doublet chemotherapy. Outcomes assessed were overall survival (OS) and radiologic responses by RECIST.

Significant correlations (Spearman ρ) were noted for fatigue and anorexia with all other BSs. Dyspnea differed significantly among groups on the basis of either the simplified comorbidity score or Charlson comorbidity index. Median OS was 287 days (95% CI, 232 to 342 days). OS was significantly higher for anorexia VAS score less than 4 (388 v 229 days for VAS score ≥ 4), fatigue VAS score less than 3 (388 v 213 days for VAS score ≥ 3), WL less than 5% (410 v 259 days for WL ≥ 5%), and MRC dyspnea grade less than 3 (377 v 187 days for MRC grade ≥ 3). On univariable Cox proportional hazards analysis, worse OS was noted for all BSs, stage, and performance status, but on multivariable analysis, only fatigue (hazard ratio [HR], 1.21), Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 1.57), and stage IV disease (HR, 1.61) were significant. Nonresponders (stable disease and progressive disease [PD]) had a higher percentage of WL and higher mean VAS scores for cough, chest pain, anorexia, and fatigue. On multivariable logistic regression analysis, PD was associated with fatigue and percentage of WL.

BSs are prognostic for patients with lung cancer on first-line chemotherapy. Fatigue is prognostic for worse OS and PD. Comorbidity and investigation profiles do not correlate with either OS or response rates.

Pemetrexed is the preferred treatment of nonsquamous non-small cell lung cancer (ns-NSCLC). Folic acid supplementation (FAS) (350 to 1000 μg daily PO) is recommended to minimize hematological toxicity (HTox). Elevated total plasma homocysteine (tpHcy) predicts increased risk of HTox with pemetrexed in absence of FAS. The current study aimed to assess prevalence of elevated tpHcy levels at baseline and after pemetrexed treatment. Association of graded tpHcy levels/FAS with toxicity was also assessed.

Retrospective analysis of all ns-NSCLC patients undergoing first-line treatment with pemetrexed-containing platinum doublet over 3½ years was carried out. All eligible patients received pemetrexed (500 mg/m) and cisplatin (65 mg/m) each on D1 of a 3-week cycle. FAS was 400 μg for tpHcy< upper limit of normal (ULN), 700 μg for tpHcy 1 to 2 ULN, and 1000 μg for tpHcy>2 ULN. All patients also received oral ferrous sulphate and injectable vitamin B12. Exact 95% confidence intervals (CI) were calculated for comparison with previously published studies.

75.7% of 111 patients had stage IV disease. Prevalence of tpHcy levels 2 ULN were 47.8%, 41.4%, and 10.8% pretreatment and 78.9%, 21.1%, and 0% posttreatment, respectively (P<0.0001). Incidence of any grade and grade 3/4 HTox was 87.4% and 17.1% (anemia), 53.2% and 7.2% (leukopenia), 36.9% and 10.8% (neutropenia), and 39.6% and 7.2% (thrombocytopenia), respectively. HTox, non-HTox, and radiologic responses did not differ among patient groups based upon baseline tpHcy levels or upon graded baseline FAS. Incidence of grade 3/4 anemia was higher in current (17.1%; 95% CI, 11.3%-25.2%) as compared with previous studies.

Prevalence of elevated tpHcy levels posttreatment as compared with baseline was reduced significantly with FAS. Among ns-NSCLC patients treated with pemetrexed and with FAS of 400 to 1000 μg daily, HTox was not associated with either baseline tpHcy levels or with graded baseline FAS.

Adenocarcinoma is the most prevalent histological type of lung cancer (LC) in developed countries while squamous cell carcinoma (SqCC) has so far been the most common type at our center. Herein, we report our continued assessment of the epidemiological trend of LC aimed at determining any change in the histological distribution.

Retrospective analysis involving all consecutive newly diagnosed LC patients over a 4-year period (March 2011-February 2015). Demographic characteristics, histology, and staging data for current data set were compared with our previously published data (2008-2011). As before, smoking index (SI) was used to group patients as never (SI = 0), light (SI = 1-100), moderate (SI = 101-300), and heavy (SI ≥301) smokers.

Majority of 1301 patients had advanced disease (Stages IIIB = 30.1%; IV = 53.3%), were males (82.3%) and current/ex-smokers (76.9%). Adenocarcinoma and SqCC (36.4% each) were equally prevalent. As compared to our previous study, adenocarcinoma increased (36.4% vs. 27.5%) and nonsmall cell lung cancer-not otherwise specified (NSCLC-NOS) decreased (5.1% vs. 10.9%) significantly (P < 0.001). The current study had more heavy smokers (68.3% vs. 61.1%; P = 0.013) and median SI was also higher (500 vs. 400; P = 0.001). Among SI-based groups, significant differences were observed for age, gender, body mass index, histology, TNM stage, and metastatic disease distribution.

Reduction in NSCLC-NOS has led to adenocarcinoma and SqCC being equally prevalent at our center in North India despite an increase in heavy smokers. Accurate histological NSCLC subtyping is necessary for optimal epidemiological assessment.

To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma (LNEPSCC).

Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions.

The systematic literature review yielded eight descriptions (n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven (64.7%) patients had limited disease (LD) and six (35.3%) had extensive disease (ED) at presentation. Chemotherapy (n = 6, 35.3%) or surgery (n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12 (70.6%) of the patients. Median (interquartile range) progression free survival and overall survival was 15 (7-42) mo and 22 (12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy.

LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.

Lung cancer, the deadliest cancer worldwide, is of particular concern in Latin America. The rising incidence poses a myriad of challenges for the region, which struggles with limited resources to meet the health care needs of its low- and middle-income populations. In this environment, we are concerned that governments are relatively unaware of the pressing need to implement effective strategies for screening, diagnosis, and treatment of lung cancer. The region has also been slow in adopting molecularly-based therapies in the treatment of advanced disease: testing for epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements are not routine, and access to targeted agents such as monoclonal antibodies and tyrosine kinase inhibitors is problematic. In this paper, we review the current situation in the management of lung cancer in Latin America, hoping that this initiative will help physicians, patient associations, industry, governments, and other stakeholders better face this epidemic in the near future.

There is limited Indian data on epidermal growth factor receptor (EGFR) gene activating mutations (AMs) prevalence and their clinicopathologic associations. The current study aimed to assess the relationship between EGFR AM and histologic subtypes and their impact on overall survival (OS) in a North Indian cohort.

Retrospective analysis of nonsmall cell lung cancer patients who underwent EGFR mutation testing (n = 186) over 3 years period (2012-2014). EGFR mutations were tested using polymerase chain reaction amplification and direct sequencing. Patients were classified as EGFR AM, EGFR wild type (WT) or EGFR unknown (UKN). Histologically adenocarcinomas (ADC) were further categorized as per the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society-2011 classification.

Overall EGFR AM prevalence was 16.6%. The ratio of exon 19 deletions to exon 21 L858R mutations was 3.17:1. Female sex (P = 0.002), never smoking status (P = 0.002), metastatic disease (P = 0.032), and nonsolid subtype of ADC (P = 0.001) were associated with EGFR AM on univariate logistic regression analysis (LRA). On multivariate LRA, solid ADC was negatively associated with EGFR AM. Median OS was higher in patients with EGFR AM (750 days) as compared to EGFR-WT (459 days) or EGFR-UKN (291 days) for the overall population and in patients with Stage IV disease (750 days vs. 278 days for EGFR-WT, P = 0.024). On univariate Cox proportional hazard (CPH) analysis, smoking, poor performance status (Eastern Cooperative Oncology Group ≥ 2), EGFR-UKN status, and solid ADC were associated with worse OS while female sex and lepidic ADC had better OS. On multivariate CPH analysis, lepidic ADC (hazard ratio [HR] =0.12) and EGFR-WT/EGFR-UKN (HR = 2.39 and HR = 3.30 respectively) were independently associated with OS in separate analyses.

Histologic subtyping of ADC performed on small biopsies is independently associated with EGFR AM and with better OS. EGFR AM presence is a positive prognostic factor for OS.

Limited data is available on comorbidity assessment in patients with lung cancer. The present prospective study assessed the prevalence and association of the Charlson comorbidity index (CCI) and simplified comorbidity score (SCS) with clinical outcomes in patients with newly diagnosed lung cancer undergoing chemotherapy.

All patients received histology-guided platinum doublets. The outcomes assessed were overall survival (OS), radiologic responses using Response Evaluation Criteria in Solid Tumors and toxicity using the Common Toxicity Criteria, version 3.0. The groups analyzed were SCS ≤ 9 (n = 173) and > 9 (n = 65) and CCI = 0 (n = 88), 1 (n = 97), and ≥ 2 (n = 53). Correlations of the CCI and SCS were assessed using Spearman's (rho) method. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the factors affecting OS using Cox proportional hazard (CPH) modeling.

Most patients had advanced disease (stage IIIB in 33.6%, stage IV in 42.4%). The median SCS was 7 (interquartile range, 7-11), and the median CCI was 1 (interquartile range, 0-1). The correlation between the CCI and SCS was moderate (rho = 0.474; P < .001). Age correlated weakly with both SCS (rho = 0.293; P < .001) and CCI (rho = 0.205; P < .001). The SCS > 9 group (vs. SCS ≤ 9) had a significantly older mean age, patients aged ≥ 70 years, men, smokers, and squamous cell histologic type. The mean age in the CCI groups was 55.2 years for a CCI of 0, 59.6 years for a CCI of 1, and 60.3 years for a CCI of 2, with a statistically significant difference (P = .002). The radiologic responses and toxicity profiles were similar between the SCS and CCI groups. The median OS was 287 days (95% CI, 232-342 days) and did not differ between the SCS and CCI groups. On multivariate CPH analyses, worse OS was independently associated with stage IV disease (adjusted HR, 2.0; 95% CI, 1.4-2.7) and poor performance status (Eastern Cooperative Oncology Group score ≥ 2; adjusted HR, 1.8; 95% CI, 1.1-2.8) but not with comorbidity, histologic type, or age.

The SCS and CCI scores correlated moderately with each other and weakly with age. The presence of comorbidities did not adversely influence clinical outcomes in this Indian cohort of lung cancer patients undergoing first-line chemotherapy.

Usefulness of total plasma homocysteine for predicting toxicity from and optimal duration of folate and vitamin B12 supplementation prior to initiation of pemetrexed-based chemotherapy both remain debatable issues following publication of recent data that challenge conventional protocols followed for the same. Randomized trials are needed in an attempt to simplify supportive care schedule during administration of pemetrexed-based chemotherapy for non-squamous NSCLC.

Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.

Clinical significance of tumor cavitation (TC) prior to and following first-line chemotherapy of lung cancer is unclear. An evaluation of the incidence and prognostic role of TC among treatment naive lung cancer patients undergoing chemotherapy at a tertiary care institute in North India was undertaken. Retrospective data analysis and radiological review of newly diagnosed lung cancer patients initiated on chemotherapy over a 2-year period were carried out. Demographic characteristics and overall survival (OS) were compared between patients with and without TC at baseline. Patients who received 3 or more cycles of chemotherapy were included in analysis for response rates and new onset TC. Overall, 27 (7.8 %) of 347 patients had baseline TC. Among 271 non-small cell lung cancer (NSCLC) patients with (n = 26) and without (n = 245) baseline TC, histology was the only demographic characteristic that differed significantly [squamous 76.9 vs. 46.9 %; p = 0.004]. Majority (82.7 %) of NSCLC patients had advanced (stage IIIB/IV) disease. NSCLC patients with and without baseline TC alive at 6 months, 1 and 2 years were 34.6 versus 53.9 %, 11.5 versus 25.7 % and 3.8 versus 7.8 %, respectively. NSCLC patients with baseline TC had shorter median OS than those without (174 days [95 % confidence interval (CI) 106-242 days] vs. 235 days [95 % CI 207-263 days]). On multivariate Cox proportional hazard analysis, age [hazard ratio (HR) = 1.02, 95 % CI 1.01-1.04] and baseline TC [HR = 1.66, 95 % CI 1.03-2.69] were found significant. Response rates were similar between the two groups. Patients with TC after chemotherapy differed from those without in frequency of squamous histology (77.8 vs. 38.9 %; p < 0.001) and presence of metastatic disease (19.4 vs. 40.9 %; p = 0.016). Squamous histology has a significant association with presence of baseline TC and of new onset TC after chemotherapy. Presence of baseline TC has an independent association with shorter OS among NSCLC patients undergoing first-line chemotherapy.

Malignancy per se and cytotoxic chemotherapy given for its treatment both are recognised risk factors for the development of tuberculosis (TB). However, individual case descriptions of pleural tuberculosis (TB-PE) following chemotherapy for lung cancer (LC) have not been published previously. We herein report the first two cases of histopathologically proven TB-PE following LC chemotherapy. The first patient was a 38-year-old man with stage IV non-small cell LC (adenocarcinoma) who developed TB-PE following four cycles of chemotherapy (pemetrexed-cisplatin). The second patient was a 49-year-old man with extensive disease small cell LC who developed TB-PE after six cycles of chemotherapy (irinotecan-cisplatin). In both patients, diagnosis of TB-PE was established by demonstration of granulomatous inflammation, caseous necrosis and positive stain for acid-fast bacilli in pleural biopsy specimens. Both cases responded to standard four-drug antitubercular therapy. These cases highlight the importance of carrying out an extensive evaluation for exudative pleural effusions in LC patients receiving chemotherapy, especially in countries with high TB prevalence. Attributing such pleural effusions to disease progression, without histopathological confirmation, may be associated with disastrous consequences.