Short-course Chemotherapy Research Articles

Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives.

Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field.

Tuberculosis and COVID-19 in Children and Adolescents. Two Waves of the Pandemic: Experiences and Conclusions

The objective of the study: to investigate diagnostics, course and outcomes of COVID-19 in children and adolescents with tuberculosis in relation to the epidemic control activities.Subjects and Methods: during the pandemic of coronavirus infection (the first and second waves), 83 patients aged 2 to 17 years (41 children and 42 adolescents) were followed up. 62 (74.7%) children got infected with the novel coronavirus infection among 82 patients treated at the clinic over this time.Results. COVID-19 has been found to be highly contagious in the group of children staying in the ward, employees working with children and adolescents were the source of infection. Compliance with sanitary and infection control activities allows reducing the likelihood of the viral infection spread in the group of children and adolescents. The respiratory syndrome is not a major sign for the diagnosis of COVID-19 in children and adolescents with respiratory tuberculosis. For the diagnosis of COVID-19, targeted immunological and microbiological tests are important. Most patients with clinical manifestations of the coronavirus infection (79.4% of cases) were diagnosed with a mild course of the disease. Co-infection (tuberculosis and COVID-19) caused no mutual aggravation. No adjustment of chemotherapy was required, and the duration of treatment didn’t increase including short-course chemotherapy regimens with multiple/extensive drug resistant Mycobacterium tuberculosis and in patients after surgery.

Genetic Variants and Drug Efficacy in Tuberculosis: A Step toward Personalized Therapy.

Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.

Short-course radiotherapy and chemotherapy for conversion surgery in patients with unresectable metastatic rectal cancer: a preliminary case series study.

Curative treatment is challenging in patients with locally advanced rectal cancer and unresectable metastases. The aim of this study was to evaluate the clinical outcomes of short-course radiotherapy (RT) followed by systemic chemotherapy for patients with rectal cancer with mesorectal fascia (MRF) involvement and unresectable distant metastases. The study included consecutive patients diagnosed as having metastatic mid-to-low rectal cancer treated with short-course RT followed by systemic chemotherapy for conversion radical or palliative surgery between 2014 and 2019 at Gil Medical Center. The patients had primary rectal tumors involving the MRF and unresectable distant metastases. The treatment strategies were determined in a multidisciplinary team discussion. Seven patients (five men and two women) underwent short-course RT (5×5 Gy) and preoperative systemic chemotherapy. The median age was 68 years (range, 46-84 years), and the median distance from the anal verge to the primary tumor was 6.0 cm (range, 2.0-9.0 cm). During the median follow-up period of 29.4 months, three patients underwent conversion radical surgery with R0 resection, two underwent palliative surgery, and two could not undergo surgery. No postoperative major morbidity or mortality occurred. The patients who underwent conversion complete radical surgery showed good long-term survival outcomes, with an overall survival time of 29.4-48.8 months and progression-free survival time of 14.7-41.1 months. Short-course RT followed by systemic chemotherapy could provide patients with unresectable stage IV rectal cancer a chance to undergo to conversion radical surgery with good long-term survival outcomes.

Short-course radiotherapy and consolidation chemotherapy: in search of a balanced protocol.

Short-course radiotherapy and consolidation chemotherapy: in search of a balanced protocol.

Efficacy of Short Term Intermittent Chemotherapy in DOTS Regimen in Extra Spinal Tuberculosis

Noncompliance is one of the major issues with the treatment of tuberculosis (TB), which can lead to treatment failure. A short-course of chemotherapy as recommended by World Health Organization under the umbrella term of Directly Observed Treatment Short Course (DOTS) therapy seems to be effective. The main aim in present study was done to evaluate the efficacy of short term intermittent chemotherapy in DOTS regimen in patients with extra spinal osteoarticular TB. The present prospective study was conducted in the Department of Ortho & Spine Surgery, National Institute of Traumatology & Orthopaedic Rehabilitation (NITOR), Dhaka, Bangladesh over a period of one year between January 2018 to February 2019. 21 patients included in our Study. All the patients were given the DOTS regime as recommended by WHO and followed up at intervals of one month during the treatment for assessing the clinical improvement and compliance of the patient. The results in present study, there were 85.71% males and 14.29% were females. 42.86% were students followed by the labourer (28.57%). Hip (47.62%) was the most commonly involved joint followed by short bones of hand and foot (19.5%). All (100%) patients had an elevated ESR at the time of presentation. Eighty percent patients had shown increase in weight at the end of 6 month of treatment. All patients of extra spinal osteoarticular TB showed improvement. Treatment was found sufficient for 80% of the patients. In 20% cases treatment duration was extended. In discussion the Short term intermittent chemotherapy in DOTS regimen was optimum for the treatment of extra spinal osteoarticular TB and was associated with good compliance.

Is 6 Months of Antitubercular Chemotherapy as Effective as More Than 6 Months Regimen in Spinal Tuberculosis? A Systematic Review and Meta-analysis.

Historically, osteoarticular tuberculosis (TB), including spinal TB, was treated with prolonged course of antitubercular therapy (ATT). Due to various challenges, there has been reluctance to explore the use of short-course ATT in spinal TB. However, with the success of short-course ATT being demonstrated in other forms of extrapulmonary TB, the subject is open for debate again. Therefore, we systematically reviewed various published literature to determine whether short-course treatment regimen (6 months) of ATT provides equivalent results in terms of disease healing as long-course treatment regimen (≥9 months) in the management of spinal TB. Five electronic databases (PubMed, MEDLINE, EMBASE, CENTRAL, and Web of Science) and their reference lists were searched to identify relevant randomized controlled trials with at least 1 year of follow-up that compared short-course with standard-course ATT for treatment of spinal TB. The methodological quality of included studies was assessed, and their data were extracted. A meta-analysis was used to calculate pooled effect sizes and 95% confidence interval (CI). The outcome measure was healed status of the disease at the final follow-up. Of 331 publications identified through literature search, eight publications describing six randomized studies were included. Moreover, 375 of 414 patients (90.58%) who received 6 months of ATT had healed status at their final follow-up compared to 404 of 463 patients (87.26%) who received ≥9 months of ATT. Overall, the healed status of spinal TB was equivalent in patients in both groups (pooled relative risk, 0.98; 95% CI, 0.92-1.04; p =0.439). However, there was considerable heterogeneity among the trials (I2=40.8%, p =0.149). The results suggest that the use of short-course (6 months) chemotherapy may be considered for the treatment of spinal TB in view of the similarity in the healing response achieved compared to treatment regimens of longer duration.

Efficacy of integrating short-course chemotherapy with Chinese herbs to treat multi-drug resistant pulmonary tuberculosis in China: a study protocol

BackgroundTuberculosis (TB) caused Mycobacterium tuberculosis (M.tb) is one of infectious disease that lead a large number of morbidity and mortality all over the world. Although no reliable evidence has been found, it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect.MethodsMulti-drug resistant pulmonary tuberculosis (MDR-PTB, n = 258) patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group (n = 172) or control/placebo group (n = 86). The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules (1 + 3 granules), while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo (1 + 3 placebo granules). In addition, MDR-PTB (n = 312) patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment (n = 208) or control/placebo (n = 104) group. The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules (2 + 4 granules), while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo (2 + 4 placebo granules). The primary outcome is cure rate, the secondary outcomes included time to sputum culture conversion, lesion absorption rate and cavity closure rate. BACTEC™ MGIT™ automated mycobacterial detection system will be used to evaluate the M.tb infection and drug resistance. Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data.DiscussionThe treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects. Chinese herbs have been used for many years to treat MDR-PTB, but are without high-quality evidence. Hence, it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB. Therefore, this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases. It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients.Trial registrationThis trial was registered at ClinicalTrials.gov (ChiCTR1900027720) on 24 November 2019 (prospective registered).Graphical

Favorable Outcomes of Patients with Limited-Stage Ocular Adnexal DLBCL Treated in the Rituximab Era: Long-Term Follow-up of a Single Center Experience

Favorable Outcomes of Patients with Limited-Stage Ocular Adnexal DLBCL Treated in the Rituximab Era: Long-Term Follow-up of a Single Center Experience

Oligometastatic Rectal Adenocarcinoma Treated With Short-Course Radiotherapy and Chemotherapy with Non-Operative Intent of the Primary for Pelvic Complete Responders

Sequential short-course radiotherapy and chemotherapy (SCRT-CH) is a promising treatment for non-operative management of rectal adenocarcinoma. This paradigm has not been evaluated for newly diagnosed oligometastatic (OM1) patients (pts). We evaluated rates of locoregional clinical complete response (cCR), rectal surgeries, and local control (LC) in newly diagnosed OM1 pts treated with definitive treatment of the primary tumor with SCRT-CH with non-operative intent for pts with locoregional cCR.From 2/2018 to 5/2020, 39 pts with newly diagnosed OM1 rectal cancer were treated with SCRT-CH and non-operative intent for locoregional cCR at a single institution. OM1 disease was considered disease confined to ≤ 2 distant sites. Pts received 25 Gy/5 fx to the pelvis with an optional boost to 35 Gy for involved extra-mesorectal lymph nodes. CH was delivered prior to and/or after RT. Locoregional cCR was assessed via DRE, sigmoidoscopy, and/or pelvic MRI following completion of SCRT-CH. Follow-up was calculated from RT completion. Survival was evaluated by Kaplan-Meier method and log rank test.All 39 pts with 47 distant sites completed SCRT and 36 (92%) had CH. 22 (56%) received all CH following RT, and 24 (62%) received at least 2 months of CH after RT. 33 pts received 1st line FOLFOX +/- bevacizumab (bev). 13 pts underwent low anterior resection and 2 pts underwent abdominoperineal resection. 19 pts had 23 distant sites treated. The most common distant site treated was liver and the most common modality was resection. Following SCRT, only 4 pts (10%) experienced a local failure (median 6.4 months, range 0.7-10.7 months). 6/39 experienced a pelvic cCR (15%); all cCR pts received SCRT first followed by at least 2 months of CH. Pts with a cCR were more likely to have received at least 2 months of CH following SCRT compared to patients without a cCR (100% vs. 59%, P < .05). The median follow-up for living pts was 16 months. The 1-year overall survival (OS) was 66% (95% CI: 51-84%) for all pts. Pts who received at least 2 months of CH following SCRT had an improved OS (1-year OS [95% CI]: 82% [68-100%] vs. 29% [10-84%], P < .001 by log-rank) compared to pts who did not.SCRT-CH with non-operative intent for pts in locoregional cCR is a promising treatment paradigm for OM1 rectal cancer pts.

Recent advances in testicular germ cell tumours.

Testicular germ cell tumours (TGCTs) are the most common solid tumours in young men and have an excellent overall cure rate and prognosis. In most patients, localised disease is cured by surgery alone, and a minority of patients receive short-course adjuvant chemotherapy to reduce the risk of further relapse. Also, in about 80% of patients, metastatic disease can be cured by systemic cisplatin-based chemotherapy. Unfortunately, for a proportion of patients, the disease exhibits platinum resistance and relapse occurs. Despite further lines of systemic treatment, cure can be difficult to achieve in these patients and ultimately about 20% of them will die from disease progression. Addressing the mechanisms underpinning platinum resistance is critical to improving the survival and chances of cure for these patients. This review describes the latest advances in TGCT research, focusing on the identification of novel biomarkers, genetic characteristics and exploring novel treatments.

Pragmatic use of short-course radiotherapy, chemotherapy and surgery for stage IV rectal cancer with locally advanced or symptomatic primary tumours.

We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

A phase II trial of short-course Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) for high tumor burden ovarian cancer: updated report with preliminary survival outcomes

<h3>Objectives:</h3> To present an updated report with preliminary survival outcomes from our feasibility study. <h3>Methods:</h3> This study was a non-randomized, open-label, multi-center, single-arm trial on the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by fast-track cytoreductive surgery (CRS) plus short-course HIPEC (i.e.: 30 min) in advanced ovarian cancer (NCT02249013). HIPEC was performed according to the closed-abdomen technique using a concentration-based regimen of cisplatin (25 mg/m²/L) or cisplatin plus doxorubicin (15mg/L) at 41–43°C. Dextrose perfusate was circulated using the Performer HT device (RAND Srl, Medolla, MO, Italy) at a flow rate of 700ml/min. Primary endpoint was PD9 (i.e.: proportion of patients with disease progression or death occurring within 9 months of interval CRS plus HIPEC) and secondary endpoints were morbidity (mortality and complication rates related to CRS plus HIPEC), time to start adjuvant chemotherapy, length of ICU and hospital stay, QoL over treatment (EORTC QLQ-C30), and ultimately progression-free (PFS) and overall (OS) survivals. Funding sources were from Decit/SCTIE/MS - CNPq/FACEPE/SES-PE (APQ:0187-4.01/13) and FAPE/IMIP. <h3>Results:</h3> A total of 15 patients with stage III epithelial malignancies were recruited from our public health system between February 2015 and July 2019 in four Brazilian centers. The median (range) age was 46 years (19–67), with preoperative serum CA125 levels of 737.7U/mL (161.6–6550). The median number of preoperative cycles of IV chemotherapy was 3 (2–4), resulting in PCI scores of 11 (3–18) at the time of interval CRS plus HIPEC performed after a median of 29 days (26–43) from the last neoadjuvant cycle. Time to restarts IV chemotherapy was 39 days (31–74) and fourteen (93.3%) patients completed all the six cycles of IV chemotherapy as planned. Only 1 patient did not start the systemic adjuvant therapy due to poor recovery after surgery. Median operation time was 490 minutes (235–865), with 9 (60%) patients requiring major bowel resection as rectosigmoidectomy (n=8) or partial colectomy (n=1), but with a nil rate of ostomies. Median length of hospital stay was 5 days (3–10), with ICU stay of 1 day (1–5). Four patients experienced no postoperative complications, whereas 5 suffered only minor G1/G2 complications, and 6 suffered major G3 complications, according to the NCI/CTCAE classification. The most common complications were electrolytes imbalance and anemia. Two patients experienced reoperation because of G3 postoperative hemorrhage or peritoneal infection, whereas no deaths were recorded. No significant difference over time in the QLQ-C30 summary scores was observed (p>0.05). With a median follow-up of 32 (18.2–61.2) months, PD9 and median PFS was 6.7% and 18 months, respectively. At this time, median OS was not reached and our 2y- PFS and OS was 30.8% and 92.8%, respectively. <h3>Conclusions:</h3> We confirm the preliminary hypothesis of safety and efficacy for our comprehensive approach involving the use of short-course HIPEC in high tumor burden ovarian cancer. Median overall survival is pending to confirm short-course HIPEC at the time of interval CRS as a promising approach in terms of survival outcomes.

Efficacy of a Short Course of Chemotherapy with ABVD for Elderly Patients with Hodgkin Lymphoma for All Disease Stages

INTRODUCTIONTreatment of classical Hodgkin's lymphoma (cHL) in the elderly population remains a challenge. Prevalence of co morbidities, increased toxicity to standard treatments, and the lack of inclusion within clinical trials contribute to this phenomena. Results are often inferior compared to young adults, and there is a paucity of evidence regarding valid treatment approaches. Recently, the GATLA HL-05 protocol has reported the results of a PET/CT-adapted strategy after 3 cycles of ABVD, regardless of stage at presentation and without upper age limit for inclusion1.METHODSIn order to evaluate the outcome of elderly patients included in this trial, a retrospective analysis was conducted on the HL-05 database. Patients (pts) equal or older than 60 years with a recent diagnosis of cHL and a negative HIV status were considered. Progression-free survival (PFS) was defined as time from treatment to relapse or death from any cause. Overall survival (OS) was defined as time from treatment to death from any cause. The Kaplan-Meier and Log-rank test method were used for survival curves. The Pearson test was applied for comparison of variables within charts. An α level of 0.05 was regarded as significant.RESULTSOf a total 377 pts enrolled within HL-05, 43 met inclusion criteria. With a median age of 66 y, 90% had a performance status of 1-2. Nodular sclerosis was the most frequent histological subtype (60% of pts), and 72% of pts were early stage (I-II, non-bulky disease). All pts received initial therapy with 3 cycles of ABVD and underwent evaluation with a PET/CT scan: 81% achieved a negative scan (Deauville scores 1-2). Of the remaining 19% positive scans, 12% were compatible with PR and 7% with PD. No grade III / IV toxicity events or treatment related deaths were reported. Within a follow-up period of 68 months, median PFS and OS have not yet been reached, and PFS was 88% at 36 months.CONCLUSIONSWith a PET/CT-adapted therapy after 3 cycles of ABVD for 43 pts older than 60 years, 81% of pts reached a negative scan and thus received no further treatment. These pts had an excellent outcome with a PFS of 88% at 3 years. The implementation of a PET/CT-guided strategy, regardless of stage at presentation, achieved excellent outcomes with a well tolerated treatment with reduced exposition to chemo and radiotherapy. Furthermore, in this study it was possible to validate the prognostic significance of achieving an early negative PET/CT within the elderly population.CITATIONS1. Pavlovsky A, Fernandez I, Kurgansky N et al. PET/CT adapted therapy after 3 cycles of ABVD to all stages of Hodgkin Lymphoma: GATLA trial HL-05. Oral Presentation. Abstract S108. EHA 2016 - Copenhagen. [Display omitted] DisclosuresPavlovsky:TAKEDA: Speakers Bureau.

A phase 2, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of KN046 in combination with chemotherapy in subjects with advanced non-small cell lung cancer.

9060 Background: Dual blockade of PD-1 and CTLA-4 has shown improved overall survival (OS) in combination with a short course of chemotherapy. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86. We hypothesized that KN046 could be combined with a full course of chemotherapy and build more durable clinical benefit. Methods: This study enrolled systemic treatment naive, stage IV NSCLC patients (pts). Eligible pts received KN046 plus platinum doublet chemotherapy until progressive disease, unacceptable toxicity, withdrawal of informed consent or death. Efficacy evaluation was performed by investigators per RECIST 1.1. Safety and tolerability were assessed per NCI-CTCAE v5.0. Results: As of the Jan. 19, 2021, 87 pts [Cohort 1 (n = 51), Cohort 2 (n = 36)] have been enrolled with 83 pts having tumor PD-L1 expression data (PD-L1 ≥1%: 55.4%; PD-L1 &lt; 1%: 44.6%). 33.3% pts remained on the study treatment and 66.7% pts discontinued treatment due to disease progression (27.6%), TEAE (13.8%), death (9.2%) and other reasons (16%). The median treatment duration of KN046 was 21 weeks (range: 1.6̃68.7 weeks). Treatment related TEAE (TRAE) occurred in 92% pts. 25.3% pts experienced Grade≥3 TRAE [diarrhoea (5.7%), alanine aminotransferase increased (4.6%), infusion related reaction (3.4%), rash (3.4%), aspartate aminotransferase increased, dermatitis allergic and immune-mediated pneumonitis (2.3%, respectively), anaphylactoid reaction, autoimmune hepatitis, back pain, bilirubin conjugated increased, hypertension, neutrophil count decreased, platelet count decreased, pneumonitis, rash maculo-papular, septic shock and white blood cell count decreased (1.1%, respectively). In 81 efficacy evaluable pts, the overall objective response rate (ORR) was 50.6% (95% CI: 39.3%,61.9%) and disease control rate (DCR) was 87.7% (95% CI: 78.5%-93.9%). The ORR and DCR in pts with non-squamous NSCLC (n = 48) were 45.8% (95% CI: 31.4%, 60.8%) and 89.6% (95% CI: 77.3%, 96.5%). The ORR and DCR in pts with squamous NSCLC (n = 33) were 57.6% (95% CI: 39.2%, 74.5%) and 84.8% (95% CI: 68.1%, 94.9). Progression free survival (PFS) and OS events have occurred in 53% and 18% patients. Median PFS was 5.9 (95%CI: 5.3, 8.7) months. Median OS was not reached. OS rate at 12 and 15 months were both 74.9%. Similar OS curves have been observed in PD-L1 ≥1% and PD-L1 &lt; 1% pts. In PD-L1 ≥1% patients, median PFS was 6.7 months (10.8 months for PD-L1 ≥1% squamous NSCLC pts). Conclusions: KN046 combined with platinum doublet chemotherapy is tolerated and has shown promising clinical benefit as IL treatment for stage IV NSCLC particularly in PD-L1≥1% tumors and squamous histology. Pivotal Phase III trial in advanced unresectable or metastatic squamous NSCLC is currently ongoing. Clinical trial information: NCT04054531.

Repeat sequential oxaliplatin-based chemotherapy (FLOX) and nivolumab versus FLOX alone as first-line treatment of microsatellite-stable (MSS) metastatic colorectal cancer (mCRC): Initial results from the randomized METIMMOX study.

3556 Background: Immune checkpoint blockade (ICB) has revolutionized patient outcome for the small mCRC subgroup with highly immunogenic disease. The majority of mCRC cases, however, are MSS without innate ICB susceptibility. In our ongoing METIMMOX study, we hypothesize that MSS mCRC can be transformed into an immunogenic condition by short-course oxaliplatin-based therapy (FLOX), enabling patients with unresectable, previously untreated metastases to obtain durable disease control when adding ICB therapy. Here we present the protocol-planned interim analysis. Methods: Eligibility criteria include infradiaphragmatic metastasis and C-reactive protein &lt; 60 mg/L. At analysis 15 January 2021, 54 patients stratified according to primary tumor sidedness and mutational status and evaluable for the primary end point (progression-free survival; PFS) had been randomly assigned to a standard-of-care schedule of 8 FLOX cycles Q2W (control arm) or repeat sequential 2 FLOX cycles and 2 nivolumab cycles (240 mg Q2W) to a total of 8 cycles (experimental arm), for both arms before treatment break until disease progression and reintroduction of a new treatment sequence. Radiologic response assessment is every 8 weeks. Safety, tolerability, objective response rate, and duration of response are among secondary end points. Results: At median follow-up of 6.4 (range, 0.5-20) months, patients were well balanced between the treatment arms with regard to the predefined strata and single-organ or multiple-organ metastases. Median PFS for the entire groups of control and experimental arm patients was 5.6 (range, 0.5-15; n = 26) and 6.6 (range, 0.5-20; n = 28) months, respectively. The number of FLOX-related CTCAE grade 3 or higher adverse events, including 2 deaths after initial FLOX administration, was comparable in the two arms. Twelve immune-related grade 3-4 adverse events (no new safety signals) were recorded. In the experimental arm, 4 (16%) patients, all RAS/BRAF-mutant cases, had experienced complete response and 9 (32%) patients had ongoing objective response at 8 months. The control arm cases had 0 with complete response and 6 (23%) with ongoing objective response at 8 months, 1 of whom had proceeded to curative-intent liver surgery. Conclusions: MSS mCRC patients may hold the opportunity of ICB responsiveness evoked by short-course oxaliplatin-based chemotherapy. The search for predictive biomarkers of ICB responsiveness is ongoing in the specifically designed METIMMOX correlative study program. Clinical trial information: NCT03388190.

Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations?

Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations?

Awareness about new guidelines of national tuberculosis elimination program among medical college faculty

Background: Physicians and faculty working in Medical Colleges play a major role in tuberculosis (TB) control. Their knowledge, attitude, and practices can affect the treatment and care of TB patients significantly.Objectives: The objectives were to assess the awareness about new guidelines of National TB Elimination Program (NTEP) among medical college faculty.Methods: A cross-sectional study was carried out among 95 faculties. They were given anonymous self-administered questionnaire with 23 questions. One mark was given for each correct answer. We classified correct knowledge as score >10 and poor knowledge as score <10. Yates-corrected Chi-square was used to study the association between variables and outcomes. P 0.05 was considered as statistically significant.Results: Questions about case detection rate, cure rate, incentives to private practitioner, bedaquiline, and follow-up of patients after completion of treatment were very poorly answered (<10 persons had correct knowledge). Only 17 could answer about the fixed-dose combinations, 10 about 99 Directly Observed Treatment Short-Course (DOTS) chemotherapy, and 13 about the choice of treatment in HIV-TB. Best answered questions were about the drugs used in each DOTS category, categories of DOTS, what are multidrug-resistant TB, extensive drug-resistant TB, and definition of presumptive case of TB. Overall, 58 faculties (61.1%) had poor knowledge with a score <11. The remaining 37 (38.9%) had correct knowledge with a score 11 or more. Correct knowledge was not found to be associated with age, sex, and designation but was associated with professional experience, with higher experience being associated with poor knowledge (P < 0.05).Conclusion: Majority of the faculty in the studied medical colleges had poor knowledge about new updates/guidelines in the NTEP. Professional experience was found to be significantly associated with the correct knowledge on recent updates in NTEP.

A comparative study of factors for interruption of antitubercular treatment among defaulters in urban and rural areas of Kamrup District, Assam.

Background:Defaulting from treatment is an important challenge for tuberculosis (TB) control. As per the Revised National Tuberculosis Control Programme quarterly reports of Kamrup District (Assam), among the registered cases default rate was 13.3%(2008) & 13.1 % (2009).Objectives:To elicit reasons & factors responsible for interruption of treatment from a cohort of TB defaulters of urban & rural areas in Kamrup District.Methods:The cross-sectional study was conducted among 1/3rd of all defaulters who were put on Directly Observed Treatment Short-course chemotherapy in 2011 under 1 urban Tuberculosis Unit (TU) & 2 rural TUs of Kamrup District. From these 3 TUs, total 210 patients interrupted treatment in 2011; so 70 defaulters (35 from 1 urban TU & 35 from 2 rural TUs) were interviewed in their residences by using a pretested and predesigned schedule. Study was conducted in January - June, 2012.Results:Majority of the defaulters was illiterate (51.4%) in rural areas but in urban areas majority studied upto high school level (37.1%). Maximum defaulters were in the age group 25-44 years (55.7% in urban areas & 62.9% in rural areas). The number of defaulters decreased uniformly with increasing income in the rural areas & but not so in urban areas. More number of new cases defaulted in rural areas (82.8%) compared to urban areas (57.1%). Improvement in symptoms was found to be the most common reason (45.7% in urban areas & 40 % in rural areas), leading to treatment interruption.Conclusions:Early improvement in symptom was the most common reason leading to treatment interruption. Continuous health education should be provided to TB patients emphasizing the need to continue treatment despite early improvement in symptoms.

Treatment of Primary Central Nervous System Germinomas With Short-course Induction Chemotherapy Followed by Low-dose Radiotherapy Without a Tumor Bed Boost: Prognostic Impact of Human Chorionic Gonadotropin.

To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (β-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal β-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased β-hCG levels, those with β-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with β-hCG levels <5 mIU/mL.