Thermo-chemical behaviour of Dunaliella salina biomass and valorising their biochar for naphthalene removal from aqueous rural environment.

Thermo-chemical behavior of a microalgal biomass; Dunaliella salina was investigated through thermo-gravimetric analyses. Fully-grown D. salina biomass were subjected for biochar conversion using pyrolytic treatment at three distinct heating rates such as 2.5, 5, and 15 °C min-1. The kinetic appraisals were explained by using model-free kinetics viz., Kissinger-Akahira-Sanose, Flynn-Waal-Ozawa and Starink iso-conversional correlations with concomitant evaluation of activation energies (Ea). The Ea value is 194.2 kJ mol-1 at 90% conversion in FWO model, which is higher as compared to other two models. Moisture, volatile substances, and other biochemical components of the biomass were volatilized between 400 and 1000 K in two separate thermo-chemical breakdown regimes. Microscopic and surface characterization analyses were carried out to elucidate the elemental and morphological characteristics of the biomass and biochar. Further, the proficiency of the prepared biochar was tested for removing naphthalene from the watery media. The novelty of the present study lies in extending the applicability of biochar prepared from D. salina for the removal of a model polyaromatic hydrocarbon, naphthalene.

Molten salt mediated single-step synthesis of reusable nanostructured CaTiO3 for the removal and recovery of Sr2+: A potential adsorbent for the contaminated water bodies.

The facile synthesis approach for the adsorbent preparation and recyclability during decontamination of radioactive pollutants is a significant concern in water treatment. The objective of this study is to, synthesis via solid-state reaction of the nanostructured CaTiO3 for the removal and recovery of strontium (Sr2+) from the various water sources. The influence of the adsorption-dependent parameters including, initial concentration, adsorbent dose, pH, contact time and co-existing ions interference were investigated. The prepared adsorbent was characterized by different analytical techniques like FT-IR, SEM with EDAX, TEM, TGA-DTG, Powder XRD and BET surface analysis. The kinetic models were also used, and according to the kinetic models, a pseudo-second-order kinetic model (R2 = 0.999) was better fitted to the adsorption of Sr2+ ions onto CaTiO3 rather than pseudo-first-order kinetics, which could properly represent the observed adsorption of Sr2+. For the isotherm study, the results are best fitted to the Langmuir isotherm model (R2 = 0.98) with a maximum adsorption capacity of 102.04 mg/g. The common ions (Na+, Mg2+, Ca2+, and K+) and Sr2+ having a concentration of 1:2, 1:3, and 1:4, where 82.8, 79.5, and 68.2 % removal was achieved of Sr2+ in each respective matrix. In addition, the adsorption and corresponding recovery and removal for the different Sr2+spiked matrices in deionized water, tap water, well water, lake water, and seawater were investigated with 97, 65.6, 76.5, 73.9 and 17.8 % removal respectively. Also, the CaTiO3 showed excellent recyclability with minimal loss even after 5 consecutive recyclability cycles and >90% removal of strontium achieved. Hence, prepared nanostructured CaTiO3 could be considered a promising adsorbent for the removal and recovery of Sr2+ions from contaminated water bodies.

ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA).

In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.

Conversion of solid wastes and natural biomass for deciphering the valorization of biochar in pollution abatement: A review on the thermo-chemical processes.

This overview addresses the formation of solid trash and the various forms of waste from a variety of industries, which environmentalists have embraced. The paper investigates the negative effects on the environment caused by unsustainable management of municipal solid trash as well as the opportunities presented by the formal system. This examination looks at the origins of solid waste as well as the typical treatment methods. Pyrolysis methods, feedstock pyrolysis, and lignocellulosic biomass pyrolysis were highlighted. Explain in detail the various thermochemical processes that take place during the pyrolysis of biomass. Due to its carbon content, low cost, accessibility, ubiquitousness, renewable nature, and environmental friendliness, biomass waste is a unique biochar precursor. This study looks at the different types of biomass waste that are available for treating wastewater. This study discussed a wide variety of reactors. Adsorption is the standard method that is used the most frequently to remove hazardous organic, dye, and inorganic pollutants from wastewater. These pollutants cause damage to the environment and water supplies, thus it is important to remove them. Adsorption is both simple and inexpensive to utilize. Temperature-dependent conversions explain the kinetic theories of biomaterial biochemical degradation. This article presents a review that explains how pyrolytic breakdown char materials can be used to reduce pollution and improve environmental management.

Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

Remediation of phthalate acid esters from contaminated environment-Insights on the bioremedial approaches and future perspectives.

Phthalates are well-known emerging pollutants that are toxic to the environment and human health. Phthalates are lipophilic chemicals used as plasticizers in many of the items for improving their material properties. These compounds are not chemically bound and are released to the surroundings directly. Phthalate acid esters (PAEs) are endocrine disruptors and can interfere with hormones, which can cause issues with development and reproduction, thus there is a huge concern over their existence in various ecological surroundings. The purpose of this review is to explore the occurrence, fate, and concentration of phthalates in various environmental matrices. This article also covers the phthalate degradation process, mechanism, and outcomes. Besides the conventional treatment technology, the paper also aims at the recent advancements in various physical, chemical, and biological approaches developed for phthalate degradation. In this paper, a special focus has been given on the diverse microbial entities and their bioremedial mechanisms executes the PAEs removal. Critically, the analyses method for determining intermediate products generated during phthalate biotransformation have been discussed. Concluisvely, the challenges, limitations, knowledge gaps and future opportunities of bioremediation and their significant role in ecology have also been highlighted.

Remedial strategies for abating 1,4-dioxane pollution-special emphasis on diverse biotechnological interventions.

1,4-dioxane is a heterocyclic ether used as a polar industrial solvent and are released as waste discharges. 1,4-dioxane deteriorates health and quality, thereby attracts concern by the environment technologists. The need of attaining sustainable development goals have resulted in search of an eco-friendly and technically viable treatment strategy. This extensive review is aimed to emphasis on the (a) characteristics of 1,4-dioxane and their occurrence in the environment as well as their toxicity, (b) remedial strategies, such as physico-chemical treatment and advanced oxidation techniques. Special reference to bioremediation that involves diverse microbial strains and their mechanism are highlighted in this review. The role of macronutrients, stimulants and other abiotic cofactors in the biodegradation of 1,4-dioxane is discussed lucidly. We have critically discussed the inducible enzymes, enzyme-based remediation, distinct instrumental method of analyses to know the fate of intermediates produced from 1,4-dioxane biotransformation. This comprehensive survey also tries to put forth the different toxicity assessment tools used in evaluating the extent of detoxification of 1,4-dioxane achieved through biotransforming mechanism. Conclusively, the challenges, opportunities, techno-economic feasibility and future prospects of implementing 1,4-dioxane through biotechnological interventions are also discussed.

Pre-to-post COVID-19 lockdown and their environmental impacts on Ghoghla beach and Somnath beach, India.

Environmental impact of COVID-19 imposed lockdown (2020) and the new normal condition (2021) on two different beaches of India (Ghoghla beach, Diu and Somnath beach, Veraval) were compared with the pre-lockdown era, 2013. The lockdown phase favored the natural restoration of the beaches and showed infinitesimal values of the parameters tested when compared with the pre-lockdown regime. However, the new normal situation in 2021 opened up the accessibility of these beaches to the tourists and pilgrims resulting in significant changes of water quality. The release of diluted sewage mixed with freshwater from the Somnath town to the sea has led to the drastic change in beach water quality. The mean cadmium concentration increased drastically in beach waters (Ghoghla: 1.35, 0.28 and 7.09 µg/L; Somnath: 0.45, 0.28 and 0.58 µg/L) during pre-to-post lockdown, respectively. However, post-lockdown resulted in the rise of toxic heavy metals in the sediments of Somnath beach but Ghoghla beach remained to be pristine which may be due to the Blue Flagship status. The total number of marine bacteria was higher during 2013 and 2021 when compared during lockdown describing greater human interventions. For instance, Vibrio spp. count in Ghoghla beach water during pre-lockdown phase was 7733 CFU/mL and this value reduced to 70 and 5 CFU/mL in the lockdown and post-lockdown phases. Interestingly, the diversity of planktonic and benthic components showed a different trend from pre-to-post lockdown due to significant change in the inorganic nutrients and metal bioaccumulation. To our knowledge, this will be the first comprehensive assessment to report the environmental and ecological health of Ghoghla beach and Somnath beach during the pre-to-post lockdown.

Coraco-clavicular endobutton and fiber tape fixation for Neer's type II unstable lateral clavicular fracture: a case series with literature review.

Neer's type II lateral end clavicle fracture is inherently unstable due to coraco-clavicular ligament disruption. Timely surgery can avoid complications of conservative management. Our study is based on open reduction and fixation with double endobutton and fibre tape in 12 patients. Radiological and functional outcome were assessed using Quick DASH score and SPADI score at regular interval. All the fractures achieved both clinical and radiological union. No intra-operative or post-operative complication was noted. Functional out come and range of motion at 1-year follow-up was quite satisfactory. Open reduction and fixation with double endobutton and fibre tape for lateral end clavicle fracture is a quite rewarding surgery with less steep learning curve, economical and enough stable fixations leading to union and good functional outcome without need of re-surgery for implant removal.

Impact of 2nd wave of COVID-19-related lockdown on coastal water quality at Diu, western coast of India and role of total alkalinity on bacterial loads.

A detailed coastal water monitoring near Diu coast, western part of India was performed from October, 2020 to May, 2021 covering the 2nd lockdown time. Average monthly fluctuation from 7 different sampling stations of total 9 physico-chemical parameters such as pH, salinity, turbidity, nitrite (NO2), nitrate (NO3), ammonia (NH3), phosphate (PO4), total alkalinity and silicate were recorded. Initially, Mann-Kendall trend test for all the 9 parameters showed non-zero trend, which may be either linear or non-linear. During 2nd lockdown period, there was a fluctuation of value for parameters like pH, salinity, nitrate, nitrite and phosphate. Average total bacterial count and differential bacterial count also gradually decreased from March, 2021 sampling. Principal component analysis (PCA) plot covering all the physico-chemical parameters as well as the differential bacterial count showed a distinct cluster of all bacterial count with total alkalinity value. Subsequently, mathematical equation was formulated between total alkalinity value and all differential bacterial count. Upto our knowledge, this is the first report where mathematical equation was formulated to obtain value of different bacterial load based on the derived total alkalinity value of the coastal water samples near Diu, India.

New normal baseline data during nationwide lock down due to Covid 19 pandemic in the world's largest ship recycling yard at Alang, India.

A detailed study to generate the new normal baseline data has been carried out during nationwide lockdown (May 12 to May 16, 2020) covering sampling for ambient air, coastal water, coastal sediments, fish and bioaccumulation of heavy metals, in an around Alang, the world's biggest ship recycling yard. The lockdown data were compared with 2018 and 2019 observed data. PM10 values during lockdown were reduced by 3.75 to 4.5 times as compared with previous 2 years. Similarly, four-fold reduction of PM2.5 and SPM values was observed during lockdown. The gaseous pollutants like NO2 and O3 are within safe limit. Overall air quality index (AQI) improved significantly during lockdown. Similarly, there was drastic reduction in the majority of the nutrient parameters in the coastal water. Different heavy metal concentration in the coastal sediments samples also showed strong reduction during lockdown sampling in comparison with other two sampling. This proves that the coastal environment has its efficient self-cleaning potentials if there is considerable reduction in the anthropogenic as well as industrial activities. Diversity of phytoplankton and zooplankton also increased. The results were validated using statistical techniques like analysis of variance and least significance difference (LSD).

PARAMOUNT: Descriptive subgroup analyses of final overall survival for the phase III study of maintenance pemetrexed versus placebo following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

INTRODUCTION: The PARAMOUNT phase III trial demonstrated that pemetrexed continuation maintenance significantly reduced the risk of disease progression (hazard ratio = 0.62) and death (hazard ratio = 0.78) versus placebo in patients with advanced nonsquamous non-small-cell lung cancer. To further understand the survival data, descriptive subgroup analyses were undertaken. METHODS: Nine hundred thirty-nine patients received induction therapy (four 21-day cycles pemetrexed 500 mg/m and cisplatin 75 mg/m), after which 539 nonprogressing patients with an Eastern Cooperative Oncology Group performance status (PS) of 0/1 were randomized (2:1) to maintenance pemetrexed (500 mg/m) cycles or placebo until disease progression. RESULTS: Baseline characteristics of patients surviving for longer periods were comparable to patients surviving shorter periods, suggesting overall survival (OS) benefit for all subgroups of patients on maintenance therapy. An examination of type and severity of induction adverse events also found no association with survival duration. Response to induction (tumor response versus stable disease) was not determinate of pemetrexed maintenance OS outcome as assessed by waterfall plot and scattergrams and by the distribution of patients among various OS intervals. The length of the interval before beginning maintenance therapy (<7 days versus ≥7/≤30 days) also did not impact the survival results. PS, a known prognostic factor, was the only baseline characteristic associated with improved OS; however, both PS 0 and PS 1 patients exhibited a survival benefit from pemetrexed maintenance. CONCLUSIONS: In PARAMOUNT, the OS benefit was seen across all subgroups. Other than PS, no baseline or clinical parameter clearly identified a subgroup more likely to benefit. Maintenance treatment decisions should be made on an individual basis.

Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer.

BACKGROUND: This randomised controlled phase 2 study compared pemetrexed and erlotinib in combination with either agent alone in terms of efficacy and safety as second-line treatment in a clinically selected population of never-smokers with non-squamous non-small cell lung cancer (NSCLC). METHODS: Patients who had failed only one prior chemotherapy regimen and had Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2 were randomised to either: pemetrexed 500 mg/m(2) on day 1 plus erlotinib 150 mg daily on days 2-14; erlotinib 150 mg daily; or pemetrexed 500 mg/m(2) on day 1 of a 21-day cycle until discontinuation criteria were met. The primary endpoint, progression-free survival (PFS), was analysed using a multivariate Cox model. Firstly, a global comparison across the three arms was performed. If the global null hypothesis was rejected at a two-sided 0.2 significance level, pairwise comparisons of pemetrexed-erlotinib versus erlotinib or pemetrexed were then conducted using the same model. Statistical significance was claimed only if both global and pairwise null hypotheses were rejected at a two-sided 0.05 significance level. FINDINGS: A total of 240 patients (male, 35%; East Asian, 55%; ECOG PS 0-1, 93%) were included. A statistically significant difference in PFS was found across the three arms (global p=0.003), with pemetrexed-erlotinib significantly better than either single agent: HR=0.57, 95% confidence interval (CI): 0.40-0.81, p=0.002 versus erlotinib; HR=0.58, 95% CI: 0.39-0.85, p=0.005 versus pemetrexed. Median PFS (95% CI) was 7.4 (4.4, 12.9) months in pemetrexed-erlotinib, 3.8 (2.7, 6.3) months in erlotinib and 4.4 (3.0, 6.0) months in pemetrexed. Safety analyses showed a higher incidence of drug-related grade 3/4 toxicity in pemetrexed-erlotinib (60.0%) than in pemetrexed (28.9%) or erlotinib (12.0%); the majority being neutropenia, anaemia, rash and diarrhoea. INTERPRETATION: Pemetrexed-erlotinib significantly improved PFS compared to either drug alone in this clinically selected population. The combination had more toxicity, but was clinically manageable.

PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

PURPOSE: In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data. PATIENTS AND METHODS: In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). RESULTS: The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. CONCLUSION: Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.

Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: final results of a randomized, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN. METHODS: In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m(2) ) plus cisplatin (75 mg/m(2) ; n = 398) or placebo plus cisplatin (75 mg/m(2) ; n = 397) to assess overall survival (OS) and secondary endpoints. RESULTS: Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P = .082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors. CONCLUSIONS: Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers.

Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial.

BACKGROUND: Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin. METHODS: In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either pemetrexed (500 mg/m(2) every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373. FINDINGS: Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49-0·79; p<0·0001). The median progression-free survival, measured from randomisation, was 4·1 months (95% CI 3·2-4·6) for pemetrexed and 2·8 months (2·6-3·1) for placebo. Possibly treatment-related laboratory grade 3-4 adverse events were more common in the pemetrexed group (33 [9%] of 359 patients) than in the placebo group (one [<1%] of 180 patients; p<0·0001), as were non-laboratory grade 3-5 adverse events (32 [9%] of 359 patients in the pemetrexed group; eight [4%] of 180 patients in the placebo group; p=0·080); one possibly treatment-related death was reported in each group. The most common adverse events of grade 3-4 in the pemetrexed group were anaemia (16 [4%] of 359 patients), neutropenia (13 [4%]), and fatigue (15 [4%]). In the placebo group, these adverse events were less common: anaemia (one [<1%] of 180 patients), neutropenia (none), and fatigue (one <1%]). The most frequent serious adverse events were anaemia (eight [2%] of 359 patients in the pemetrexed group vs none in the placebo group) and febrile neutropenia (five [1%] vs none). Discontinuations due to drug-related adverse events occurred in 19 (5%) patients in the pemetrexed group and six (3%) patients in the placebo group. INTERPRETATION: Continuation maintenance with pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with pemetrexed plus cisplatin. FUNDING: Eli Lilly and Company.