Major Pathologic Response after Induction Therapy Has a Long-Term Impact on Survival and Tumor Recurrence in Stage IIIA/B Locally Advanced NSCLC

2019 ◽  
Vol 68 (07) ◽  
pp. 639-645
Author(s):  
Waldemar Schreiner ◽  
Wojciech Dudek ◽  
Ralf Joachim Rieker ◽  
Sebastian Lettmaier ◽  
Rainer Fietkau ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Lung Resection ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Pathologic Response ◽  
Perioperative Morbidity ◽  
Platinum Based Chemotherapy ◽  
Impact On Survival ◽  
Long Term Impact

Abstract Background Major pathologic response (MPR) determines favorable outcome in locally advanced non-small cell lung cancer after induction therapy (IT) followed by lung resection. The aim of this retrospective study was to identify the prognostic relevance of MPR in long-term interval. Methods In 55 patients, the survival rate according to MPR and non-MPR was estimated by Kaplan–Meier method and compared using log-rank, Breslow, and Tarone–Ware tests. Results The IT included chemoradiation with 50.4 Gy (range: 45–56.4 Gy) combined with platinum-based chemotherapy in 52 patients (94.5%) and platinum-based chemotherapy in 3 patients (5.5%). Perioperative morbidity and 30-day mortality were 36 and 3.6%, respectively. The estimated 5-year postoperative and progressive-free survivals were statistically significantly improved in MPR versus non-MPR with 53.5 versus 18% and 49.4 versus 18.5%, respectively. According to the log-rank, Breslow, and Tarone–Ware tests, the MPR demonstrates prognostic significance in early, long-term, and whole postoperative interval. Conclusion MPR is associated with a robust correlation to long-term postoperative and recurrence-free survival improvement, and can potentially simplify the multidisciplinary debate and allow further stratification of adjuvant treatment in multimodality therapy.

Induction Therapy Prior to Surgical Resection for Patients Presenting with Locally Advanced Esthesioneuroblastoma

2020 ◽  
Author(s):  
Kevin C. Miller ◽  
John P. Marinelli ◽  
Jeffrey R. Janus ◽  
Ashish V. Chintakuntlawar ◽  
Robert L. Foote ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Multidisciplinary Approach ◽  
Advanced Disease ◽  
Frozen Section ◽  
Locally Advanced ◽  
Patient Records ◽  
Term Survival ◽  
Positive Margins ◽  
Definitive Surgery

AbstractEsthesioneuroblastoma (ENB) is a rare olfactory malignancy that can present with locally advanced disease. At our institution, patients with ENB in whom the treating surgeon believes that a margin-negative resection is initially not achievable are selected to undergo induction with chemotherapy with or without radiotherapy prior to surgery. In a retrospective review of 61 patient records, we identified six patients (10%) treated with this approach. Five of six patients (83%) went on to definitive surgery. Prior to surgery, three of five patients (60%) had a partial response after induction therapy, whereas two of five (40%) had stable disease. Microscopically margin-negative resection was achieved in four of five (80%) of the patients who went on to surgery, while one patient had negative margins on frozen section but microscopically positive margins on permanent section. Three of five patients (60%) recurred after surgery; two of these patients died with recurrent/metastatic ENB. In summary, induction therapy may facilitate margin-negative resection in locally advanced ENB. Given the apparent sensitivity of ENB to chemotherapy and radiotherapy, future prospective studies should investigate the optimal multidisciplinary approach to improve long-term survival in this rare disease.

Long-term response in a patient with urothelial cancer (UC) treated with AEZS-108.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15596-e15596
Author(s):  
Gustavo L. Fernandez ◽  
Andrew V. Schally ◽  
Tulay Koru-Sengul ◽  
Merce Jorda ◽  
Jaime R. Merchan ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Drug Uptake ◽  
Investigational Drug ◽  
Cancer History ◽  
First Case ◽  
Platinum Based Chemotherapy ◽  
Severe Back Pain ◽  
Grade 3 ◽  
Term Response

e15596 Background: AEZS-108 (AN-152, zoptarelin doxorubicin) is an LHRH-cytotoxic hybrid drug consisting of a Luteinizing Hormone Releasing Hormone (LHRH) agonist coupled to the cytotoxic radical, doxorubicin. The binding permits AEZS-108 to accumulate on the surface of cells expressing LHRH receptors (LHRH-R) thus allowing drug uptake. This approach exploits LHRH-R to gain access to the targeted tumor cells. Once internalized, the cytotoxic properties of doxorubicin induce the anti-tumor response. Methods: This is a case report of a 66 year old male with a superficial bladder cancer history who was diagnosed in May 2009 with metastatic UC from the prostatic urethra. He presented with pelvic and retroperitoneal lymph nodes (LN). Patient had a partial response to cisplatin based chemotherapy and underwent radical cystoprostatectomy in Oct 2009. No residual UC in bladder or prostate was seen on pathology's examination. However he did have 11/24 removed LN positive for UC. The patient showed increased retroperitoneal LN by December 2009. He received 2 further lines of chemotherapy with no response and developed severe back pain, cervical LN, extensive liver metastases and a bulky retroperitoneal mass. The patient entered a Phase I clinical trial of AEZS-108, for “locally advanced unresectable or metastatic LHRH-R positive UC patients who failed platinum based chemotherapy“. He received AEZS-108 every 3 weeks for 9 cycles from May to October, 2011. Results: After 2 cycles of the investigational drug all pain and palpable lymph neck nodes disappeared; he stopped all narcotics and tolerated treatment very well. Mostly grade1-2 with few grade 3 toxicities were seen. CT scan pretreatment, and at 8, 22, 75 weeks post-treatment showed dramatic response at all disease sites. Twenty months after treatment start, the patient is symptom- free with no evidence of disease. Conclusions: This is the first case of a patient with LHRH-R positive Urothelial Carcinoma treated with AEZS-108 that is being reported. Considering the generally poor outcome of progressive UC and the short survival of these patients, the effect of this drug in this patient has been remarkable. The phase one study is ongoing.

ERDAFITINIB in locally advanced or metastatic urothelial carcinoma (mUC): Long-term outcomes in BLC2001.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5015-5015 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Andrea Necchi ◽  
Se Hoon Park ◽  
Jesús García-Donas ◽  
Robert A Huddart ◽  
...  
Keyword(s):  
Safety Profile ◽  
Objective Response ◽  
Locally Advanced ◽  
Optimal Schedule ◽  
Safety Data ◽  
Serum Phosphate Level ◽  
Primary Analysis ◽  
Platinum Based Chemotherapy

5015 Background: Erdafitinib (JNJ-42756493; ERDA) is the only pan-FGFR kinase inhibitor with US FDA approval for treatment of adults with mUC with susceptible FGFR3/2 alterations (alt) and who progressed on ≥ 1 line of prior platinum-based chemotherapy (chemo). Approval was based on data from the primary analysis of the pivotal BLC2001 trial1. Here we report long-term efficacy and safety data from the 8 mg/d continuous dose regimen in BLC2001. Methods: BLC2001 (NCT02365597) is a global, open-label, phase 2 trial of pts with measurable mUC with prespecified FGFR alt, ECOG 0-2, and progression during/following ≥ 1 line of prior chemo or ≤ 12 mos of (neo)adjuvant chemo, or were cisplatin ineligible, chemo naïve. The optimal schedule of ERDA determined in the initial part of the study was 8 mg/d continuous ERDA in 28-d cycles with uptitration to 9 mg/d (ERD 8 mg UpT) if a protocol-defined target serum phosphate level was not reached and if no significant treatment-related adverse events (TRAEs) occurred. Primary end point was the confirmed objective response rate (ORR=% complete response + % partial response). Key secondary end points were progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Results: Median follow-up for 101 patients treated with ERDA 8 mg UpT was ~24 months. Confirmed ORR was 40%. Median DOR was 5.98 mos; 31% of responders had DOR ≥ 1 yr. Median PFS was 5.52 mos, median OS was 11.3 mos. 12-mos and 24-mos survival rates were 49% and 31%, respectively. Median treatment duration was 5.4 mos. The ERDA safety profile was consistent with the primary analysis. No new TRAEs were seen with longer follow-up. Central serous retinopathy (CSR) events occurred in 27% (27/101) of patients; 85% (23/27) were Grade 1 or 2; dosage was reduced in 13 pts, interrupted for 8, and discontinued for 3. On the data cut-off date, 63% (17/27) had resolved; 60% (6/10) of ongoing CSR events were Grade 1. There were no treatment-related deaths. Conclusions: With a median follow-up of 2 yrs, ERDA in mUC + FGFR alt showed a manageable safety profile and consistent efficacy, with median OS of 11.3 mos. 31% had a DOR ≥12 mos and 31% were alive at 24 mos. ERDA monotherapy vs. immune checkpoint inhibitor (PD-1) or chemo is being further analyzed in a randomized control study (THOR; NCT03390504).Reference: Loriot Y, et al. N Engl J Med. 2019;381:338-48. Clinical trial information: NCT02365597 .

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Metabolic effects of bariatric surgery

2016 ◽  
Vol 174 (1) ◽  
pp. R19-R28 ◽  
Author(s):  
Ricard Corcelles ◽  
Christopher R Daigle ◽  
Philip R Schauer
Keyword(s):  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Metabolic Syndrome ◽  
Weight Loss ◽  
Metabolic Effects ◽  
Perioperative Morbidity ◽  
Increased Risk ◽  
Long Term Impact

Obesity is associated with an increased risk of type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, osteoarthritis, numerous cancers and increased mortality. It is estimated that at least 2.8 million adults die each year due to obesity-related cardiovascular disease. Increasing in parallel with the global obesity problem is metabolic syndrome, which has also reached epidemic levels. Numerous studies have demonstrated that bariatric surgery is associated with significant and durable weight loss with associated improvement of obesity-related comorbidities. This review aims to summarize the effects of bariatric surgery on the components of metabolic syndrome (hyperglycemia, hyperlipidemia and hypertension), weight loss, perioperative morbidity and mortality, and the long-term impact on cardiovascular risk and mortality.

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