Redefining success: Incorporating long-term survival outcomes into routine benchmarking

Chimeric Antigen Receptor (CAR) T cell therapy targeting CD19 has introduced a paradigmatic shift in our treatment approach for advanced B cell malignancies. A major advance has been in the field of pediatric B-ALL where complete responses have been achieved across clinical trials with rates of 65–90% in the relapsed/refractory setting. These striking early response rates led to FDA approval of Tisagenlecleucel, CD19-specific CAR T cells, in August 2017. With broadened access and available longitudinal follow up, it is imperative to study the true durability of CAR-mediated responses and establish long-term relapse free and survival outcomes following CAR therapy. Phase I and II clinical trials have reported event-free survival rates of 50% at 1 year following CD19-CAR infusion in children and young adults with B-ALL. Here, we review some of the major challenges accounting for the discrepancy between early response rates and long term outcomes. In specific, relapse with CD19+ or CD19– disease has emerged as a major challenge following CD19-CAR T cell therapy. Related, is the issue of CAR persistence which has been shown to correlate with long-term outcomes. We highlight select efforts to optimize clinical strategies and CAR design to promote enhanced persistence. To date, we do not have robust predictors of response durability and relapse following CAR therapy. The ability to identify patients at risk of relapse in an a priori manner may introduce an interventional window to consolidate CAR-mediated remissions and enhance response durability. This review highlights the need to bridge the gap between the remarkable early complete responses achieved with CD19-CAR T cell therapy and the long-term survival outcomes.

Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations.

Long-Term Surgical and Survival Outcomes of Endometrial Cancer Treated with Laparoscopic Assisted Staging Surgery

Anastomotic leak after restorative surgery for rectal cancer is a major complication and may lead to worse long-term oncological and survival outcomes. The purpose of this study was to identify risk factors associated with anastomotic leak and to assess the perioperative and long-term oncological impact of anastomotic leak in our cohort of patients with rectal cancer. A retrospective analysis was performed on data from the prospectively maintained Cabrini Monash colorectal neoplasia database. Patients who had undergone rectal cancer resection and subsequently received anastomosis between November 2009 and May 2020 were included in this study. Patient and tumor characteristics, technical risk factors, and short-term and perioperative as well as long-term oncological and survival outcomes were assessed. The study was conducted in 3 tertiary hospitals. A total of 693 patients met the inclusion criteria for this study. Univariate analyses were performed to assess the relationship between anastomotic leak and patient and technical risk factors, as well as perioperative and long-term outcomes. Univariate and multivariate proportional HR models of overall and disease-free survival were calculated. Kaplan-Meier survival analyses assessed disease-free and overall survival. Anastomotic leak rate was 3.75%. Males had an increased risk of anastomotic leak, as did patients with hypertension and ischemic heart disease. Patients who experience an anastomotic leak were more likely to require reoperation and hospital readmission and were more likely to experience an inpatient death. Disease-free and overall survival were also negatively impacted by anastomotic leaks. This is a retrospective analysis of data from only 3 centers with the usual limitations. However, these effects have been minimized because of the high quality and completeness of the prospective data collection. Anastomotic leaks after restorative surgery negatively affect long-term oncological and survival outcomes for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/C81 . ANTECEDENTES:La fuga anastomótica tras una cirugía restauradora para el cáncer de recto es una complicación mayor y puede conducir a peores resultados oncológicos y de supervivencia a largo plazo.OBJETIVO:El propósito de este estudio fue identificar los factores de riesgo asociados con la fuga anastomótica y evaluar el impacto oncológico perioperatorio y a largo plazo de la fuga anastomótica en nuestra cohorte de pacientes con cáncer de recto.DISEÑO:Se realizó un análisis retrospectivo de datos obtenidos de la base de datos Cabrini Monash sobre neoplasia colorrectal la cual es mantenida prospectivamente. Se incluyeron en este estudio pacientes que fueron sometidos a una resección del cáncer de recto y que posteriormente recibieron una anastomosis entre noviembre de 2009 y mayo de 2020. Se evaluaron las características del paciente y del tumor, los factores de riesgo relacionados a la técnica, los resultados oncológicos y de supervivencia perioperatorio, así como los resultados a corto y largo plazo.AJUSTES:El estudio se realizó en tres hospitales terciarios.PACIENTES:Un total de 693 pacientes cumplieron con los criterios de inclusión para este estudio.PRINCIPALES MEDIDAS DE RESULTADO:Se realizaron análisis univariados para evaluar la relación entre la fuga anastomótica y aquellos factores relacionados al paciente, a la técnica, así como los resultados perioperatorios y a largo plazo. Se calcularon modelos de razón de riesgo proporcional univariante y multivariante de supervivencia global y libre de enfermedad. Los análisis de supervivencia de Kaplan-Meier evaluaron la supervivencia libre de enfermedad y la supervivencia global.RESULTADOS:La tasa de fuga anastomótica fue del 3,75%. Los hombres tenían un mayor riesgo de fuga anastomótica al igual que aquellos pacientes con hipertensión y cardiopatía isquémica. Los pacientes que sufrieron una fuga anastomótica tuvieron mayores probabilidades de requerir una reintervención y reingreso hospitalario, así como también tuvieron mayores probabilidades de sufrir una muerte hospitalaria. La supervivencia libre de enfermedad y general también se vio afectada negativamente por las fugas anastomóticas.LIMITACIONES:Este es un análisis retrospectivo de datos de solo tres centros con las limitaciones habituales. Sin embargo, estos efectos han sido minimizados debido a la alta calidad y la exhaustividad de la recopilación prospectiva de datos.CONCLUSIONES:Las fugas anastomóticas después de una cirugía restauradora afectan negativamente los resultados oncológicos y de supervivencia a largo plazo para los pacientes con cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/C81 . (Traducción-Dr. Osvaldo Gauto ).

Analysis for actual mid-term (≥5 years) and long-term (≥10 years) survivors with hepatocellular carcinoma (HCC) following curative hepatectomy are rarely reported in the literature.This retrospective study aims to study the mid- and long-term survival outcome and associated prognostic factors following curative hepatectomy for HCC in a tertiary referral center.The clinical data of 325 patients who underwent curative hepatectomy for HCC were reviewed. They were stratified into 3 groups for comparison (Group 1, overall survival <5 years; Group 2, overall survival ≥5, and <10 years; Group 3, overall survival ≥10 years). Favorable independent prognostic factors for mid- and long-term survival were analyzed.A bimodal distribution of actual survival outcome was observed, with short-term (<5 years) survival of 52.7% (n = 171), mid-term survival of 18.1% (n = 59), and long-term survival of 29.2% (n = 95). Absence of microvascular invasion (OR 3.690, 95% CI: 1.562–8.695) was independent good prognostic factor for mid-term survival. Regarding long-term overall survival, young age (OR 1.050, 95% CI: 0.920–0.986), ASA grade ≤2 (OR 3.746, 95% CI: 1.325–10.587), high albumin level (OR 1.008, 95% CI: 0.920–0.986), solitary tumor (OR 3.289, 95% CI: 1.149–7.625) and absence of microvascular invasion (OR 4.926, 95% CI: 2.192–11.111) were independent good prognostic factors.Curative hepatectomy results in bimodal actual survival outcome with favorable long-term survival rate of 29.2%. Favorable independent prognostic factors (age, ASA grade, albumin level, tumor number, and microvascular invasion) are identified for overall survival.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

Bladder-sparing Treatment in Patients with Bacillus Calmette-Guerin–unresponsive Non–muscle-invasive Bladder Cancer: An Analysis of Long-term Survival Outcomes

Cetuximab and Radiation Therapy Versus Cisplatin and Radiation Therapy for Locally Advanced Head and Neck Cancer: Long-Term Survival and Toxicity Outcomes of a Randomized Phase 2 Trial

To evaluate the long-term survival and functional outcomes of patients with prolonged disorders of consciousness (pDoC) 1-8 years after brain injuries. Retrospective study to assess the long-term survival and functional outcomes of patients with pDoC was conducted. We performed Cox regression and multivariate logistic regression to calculate hazard ratios (HRs) for the outcome of survival and to identify risk factors of the functional outcome. We recruited 154 patients with pDoC. The duration of follow-up from disease onset was 1-8 years. The median age was 46 years (IQR, 32-59), and 65.6% (n = 101) of them were men. During the follow-up period, one hundred and ten patients (71.4%) survived; among them, 52 patients had a good outcome. From the overall survival curve, the 1-, 3-, and 8-year survival rates of patients were about 80.5%, 72.0%, and 69.7%, respectively. Cox regression analysis revealed a significant association between the lower APACHE II score (p = 0.005) (cut-off score ≥ 18) and the presence of sleep spindles (p = 0.001) with survival. Logistic regression analysis demonstrated a higher CRS-R score (cut-off score ≥ 7), and presence of sleep spindles were related to a favorable outcome among patients with pDoC. Sleep spindles are correlated with both long-term survival and long-term functional outcome in pDoC patients.

ABSTRACTIntroductionTherapeutic hypothermia (TH) is the neuroprotective strategy for comatose survivors of cardiac arrest. It improves neurological outcomes at hospital discharge. However, data regarding long-term outcomes are limited. We aimed to study functional ability and survival of the patients after discharge.Patients and methodsWe reviewed data of post-arrest patients undergoing TH in our hospital from 2006 to 2014 and assessed the functional ability of conscious survivors after hospital discharge by using a disability rating scale (DRS). We compared the patients' DRS after discharge with their cerebral performance category (CPC) at hospital discharge. Additionally, we analyzed survival rates at 6 months, 1, 2, and 3 years.ResultsOf 51 patients undergoing TH, 27 survived, and 17 of these were conscious. Approximately 75%, 73%, 71%, and 56% of the hospital survivors were alive at 6 months, 1, 2 and 3 years, respectively. We evaluated the functional ability (DRS) in 15 awake patients. The majority of the patients with good performance (CPC1) at discharge returned to normal function or minimal disability (DRS 0-3). Interestingly, although the patients with worse CPC scores at discharge had a greater risk of functional disability and death, a patient with severe disability (CPC3) at discharge fully recovered and was able to return to work later on.ConclusionLong-term survival of conscious patients undergoing TH was quite high. The good CPC score at discharge potentially predicted the favorable forthcoming outcome. However, it was difficult to predict the unfavorable long-term outcome from the poor condition at discharge.How to cite this articleKongpolprom N, Cholkraisuwat J. Long-term Survival and Functional Neurological Outcome in Conscious Hospital Survivors Undergoing Therapeutic Hypothermia. Indian Journal of Critical Care Medicine, January 2019; 23(1):20-26.

Liver Resection for Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

Long-Term Outcome Following Three-Dimensional Conformal/Intensity-Modulated External-Beam Radiotherapy for Clinical Stage T3 Prostate Cancer

Final Report of NRG Oncology RTOG 0022: A Phase I/II Study of Conformal and Intensity Modulated Radiation for Oropharyngeal Cancer

Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting. A total of 468 metastatic/advanced NET patients (wide range of primary sites including CUP-NETs), who underwent at least two cycles of 177Lu-DOTATATE PRRT with available follow-up information, were included and analysed retrospectively in this study. In-house labelling of DOTATATE with 177Lu (direct route produced) was carried out in the hospital radiopharmacy and treatment administered in cycles (dose: 5.55 to 7.4 GBq per patient), at 10-12 weeks interval. The assessment of long-term outcome was undertaken under three broad headings: (a) Therapeutic response, (b) Survival outcome and (c) Toxicity assessment. The median point estimate with 95% CI for progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic covariates for association with PFS and OS was investigated by Cox proportional hazards model (univariate and multivariate Hazard Ratios) and with disease control rate (DCR) by Chi-square test, with significant P value defined as <0.05. Long-term outcome (follow-up ranging from 4 to 97.6 months; median period:46 months following first 177Lu-DOTATATE PRRT) results showed, (i) on symptomatic response evaluation scale, complete response (CR) in 214 patients (45.7%), partial response (PR) in 108 (23.1%), stable disease (SD) in 118 (25.2%), progressive disease (PD) in 28 (6%). (ii) Biochemical response evaluation showed CR in 52 (12%), PR in 172 (40%), SD in 161 (38%), and PD in 42 patients (10%). (iii) Molecular imaging response (by PERCIST criteria) showed CR in 29 (6%), PR in 116 (25%), SD in 267 (57%) and PD in 56 (12%) patients. (iv) On RECIST 1.1 criteria, CR was observed in 14 patients (3%), PR in 126 patients (27%), SD in 282 patients (60%) and PD in 46 patients (10%). The median PFS and OS were not reached at a median follow-up of 46 months. Observed PFS and OS at 7 years were 71.1% 95% CI (62.4-79.7%) and 79.4% 95% CI (71.4-86.9%) respectively. PFS was dependent on previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake, site of primary tumour, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake and number of PRRT cycles. The OS was dependent on baseline 68Ga-DOTATATE uptake, site of primary tumour, presence of bony metastatic disease, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for bony metastatic disease and number of PRRT cycles. Transient haematological toxicity of Grade 1, Grade 2, and Grade 3 was found in 8 (1.7%), 1 (0.2%) and one patient (0.2%), respectively. Nephrotoxicity of Grade 1, Grade 2, Grade 3, and Grade 4 were seen in 16 (3.5%), 3 (0.6%), 2 (0.4%) and one patient (0.2%), respectively. On a separate sub-analysis of 322 NET patients with progressive disease at the initiation point of PRRT, overall response rates (CR + PR + SD) were 93.5%, 88.5%, 89.1 and 87.9% on symptomatic, biochemical, RECIST 1.1 and PERCIST criteria and PFS and OS at 7 years 68.3% and 79.2%, respectively. The present results demonstrate that 177Lu-DOTATATE PRRT improved symptoms and biochemical markers substantially in most of the NET patients, with disease stabilisation on both anatomical and molecular imaging in majority and response in a sizeable fraction. Additionally, the therapeutic protocol with lesser dose per cycle (mean 5.92 GBq/cycle) and prolonged duration (over 5 cycles and 1.5 years) in a metastatic NET setting proved equally efficacious (with superior PFS and OS rates) and relatively better tolerated with minimal toxicity. The present work critically examines the long-term results, survival outcome and toxicity profile of the indigenous 177Lu-DOTATATE (produced through direct neutron activation of enriched 176Lu) in metastatic progressive NETs across a wide range of primary sites and malignancies. Such long-term outcome data establishes the favourable impact of PRRT in a wide patient base and also the therapeutic efficacy of the product.

Long-term Outcome After Resection of Isolated Thoracic Lymph Node Metastases of Renal Cell Cancer