Performance and side effect evaluation of sequentially reduced radiotherapy doses in a phase II trial of induction chemotherapy (IndCT) followed by concomitant chemoradiotherapy (CTX) for advanced head and neck cancer (HNC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5558-5558
Author(s):  
M. A. List ◽  
E. E. Vokes ◽  
E. W. Cohen ◽  
K. M. Stenson ◽  
T. Karrison ◽  
...  
Keyword(s):  
Side Effects ◽  
Radiation Dose ◽  
Performance Status ◽  
Stage Iv ◽  
Radiation Doses ◽  
Swallowing Problems ◽  
And Performance ◽  
Group B ◽  
The University

5558 Background: CTX regimens are often limited by severe acute toxicities and long-term functional impairment. This paper presents patient (pt) reported side effects and performance outcome in 3 sequential groups of stage IV HNC pts treated at the University of Chicago with IndCT and lowering radiation doses with the goal of maintaining survival while minimizing negative sequelae. Methods: Pts. were treated with IndCT followed by alternating weeks of concurrent CTX with lowering doses of radiotherapy to gross disease/ high risk microscopic/low risk microscopic disease: Group A - 75/60/45 Gy (n = 36 pts); Group B - 75/54/39 Gy (n = 34 pts); Group C - 72/51/36 Gy (n = 60 pts), respectively (treatment details & survival analyses presented separately). Pts were assessed for quality of life, performance (Performance Status Scale for HNC) and side effects (Radiotherapy Questionnaire) pretreatment, during CTX, at 3 & 12 months and annually thereafter. Controlling for baseline scores, differences between the groups were examined on- treatment and at 12-months. Results: Baseline and 12-month data were available for 81/114 pts. While all pts declined in performance (e.g., diet) and reported increased side effects (e.g., dry mouth, mouth pain, swallowing problems) on CTX, there were no statistically significant differences based on radiation dose. Similarly, there was improvement in most symptoms by 12 months with little difference among groups. In contrast, on normalcy of diet, fewer patients in Group C (20%) showed declines of more than 20 points from baseline compared to A (46%; p = .085) and B (45%, p = .09). Overall, 4% of patients were unable to take anything orally at 12-months with no difference among groups. Conclusions: This study showed no differences in pt reported symptoms on-treatment or at 12-months based on lowered radiation doses during CXT. On the other hand, while there continued to be some restriction in long-term diet, pts in the lowest radiation dose group showed somewhat less decline from baseline. These findings suggest the continued need to explore ways of decreasing both acute and long term toxicities in the use of CTX regimens. [Table: see text]

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

RA05.08: OPTIMAL RADIATION DOSE IN THE NEOADJUVANT TREATMENT OF ESOPHAGEAL CANCER: A COMPARATIVE EUROPEAN STUDY

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 29-29
Author(s):  
Styliani Mantziari ◽  
Pierre Allemann ◽  
Michael Winiker ◽  
Marguerite Messier ◽  
Nicolas Demartines ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Esophageal Cancer ◽  
Radiation Dose ◽  
Anastomotic Leakage ◽  
Disease Free Survival ◽  
Free Survival ◽  
Group A ◽  
Group B ◽  
Disease Free

Abstract Background Current guidelines recommend the use of neoadjuvant chemo-radiation (NCR) for the treatment of locally advanced esophageal cancer, both types, adenocarcinoma (AC) and squamous cell carcinoma (SCC). So far, the optimal dose of radiotherapy to achieve a maximal tumor response within an acceptable toxicity is not yet determined. The aim of this study was to assess the impact of preoperative radiation dose on postoperative outcomes and long-term survival. Methods Consecutive patients operated in two European tertiary centers for AC or SCC, treated with NCR and surgery from 2000–2016 were assessed. Specific postoperative complications (i.e. anastomotic leakage, atrial fibrillation), histological tumor regression grade (TRG, Mandard score), overall and disease-free survival were compared among three patients groups: group A (41.4Gy), group B (45Gy), and group C (50.4Gy). The x2 or Fisher test were used for categorical variables and ANOVA for continuous variables. Survival analysis was done with the Kaplan-Meier method and log-rank test. Results There were 294 patients included; 41.5% (n = 122) had AC and 58.5% (n = 172) SCC. Overall, 9.2%/27 patients received 41Gy, 57.8%/170 patients 45Gy and 33%/97 patients received 50.4Gy. Carboplatin-Paclitaxel was the most frequently used chemotherapy for group A (62.9%), and 5FU-Cisplatin for groups B (69.4%) and C (51.5%). Postoperative anastomotic leakage was lower for group B (7.1%) compared to group A (22.2%) and C (13.4%) (P = 0.036), as was the occurrence of atrial fibrillation (11.8% group B, 33.3% group A and 19.6% group C, P = 0.013). Complete or excellent response (TRG 1–2) was significantly better for group B (58.2%), followed by group C (49.5%) and A (25.9%) patients (P = 0.012). Median overall survival was 48, 27 and 29 months for group A, B and C (P = 0.498), and median disease-free survival was 13, 27 and 18 months (P = 0.411), respectively. Conclusion Preoperative radiotherapy dose of 45Gy with 5FU-Cisplatin was associated with a better histological response and less postoperative adverse outcomes compared to 41Gy and 50.4Gy, with no significant differences in long-term recurrence and survival. The role of the type of chemotherapy and histological tumor type are important co-factors affecting outcome and must be further assessed. Disclosure All authors have declared no conflicts of interest.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Identification of a microRNA (miRNA) based signature for survival in advanced non-small cell lung cancer (NSCLC) patients (pts) treated with cisplatin-vinorelbine: A ELCWP study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18006-e18006
Author(s):  
Thierry Berghmans ◽  
Luc Willems ◽  
Marianne Paesmans ◽  
Lieveke Ameye ◽  
Jean-Jacques Lafitte ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Score ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Cox's Regression ◽  
And Performance ◽  
A Prospective Study ◽  
Nsclc Patients

e18006 Background: Main prognostic factors for survival in NSCLC pts are stage and performance status (PS) while sex, histology and others are reported. However, these variables do not allow predicting individual prognosis, justifying further research. MiRNA are small non-coding RNAs regulating gene expression. As a secondary aim of a prospective study, we looked at the prognostic value of tumour miRNA on survival in NSCLC pts treated by cisplatin (60 mg/m2 D1) and vinorelbine (25 mg/m2, D1+8) 1st line chemotherapy. Methods: During the diagnostic bronchoscopy, a biopsy was lysed into Tripure Isolation Reagent (Roche Diagnostics) on ice, snap frozen and stored at -80°C. MiRNA expression was assessed using TaqMan Low Density Arrays (756 human miRNA panel, Applied Biosystems) and normalized using the delta delta CT method to RNU48 (SNORD48) CT value for every sample. Survival was measured from the registration date. Results: The main characteristics of 38 eligible pts were: median age 60 years, male 27 (71%), 80-100 Karnofsky PS in 26 (68%), adenocarcinoma 20 (53%), stage IV 30 (79%). At time of analysis, 25 pts were dead. After stepwise selection among 756 analysed miRNA, a combination of 4 miRNA including miR-200c, miR-424, miR-29c and miR-124 provided a prognostic signature for survival. Using a linear combination of the miRNA CT values with Cox's regression coefficients as weights, we constructed a prognostic score. With a cut-off of 52, the signature distinguished pts with good (n = 18) and poor (n = 20) prognosis with respective median survival of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p <0.001; hazard ratio 21.1, 95% CI 4.7-94.9). The same signature discriminated pts with “good progression-free survival” (median 19.8 months; 95% CI 15.3-33.8) from the others (median 9.1 months; 95% CI 6.3-15.5) (p <0.001; hazard ratio 3.8, 95% CI 1.7-8.7). Conclusions: A 4 miRNA signature is associated with improved survival in patients with advanced stage NSCLC treated with 1st line cisplatin and vinorelbine. These results need confirmation in an independent cohort and the signature has to be compared to conventional prognostic factors.

OAMs at the end: The end of the beginning or the beginning of the end?

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 229-229
Author(s):  
Annemarie P Hargadon ◽  
Barbara Marie Galligan ◽  
Chintan Shah ◽  
Iris Chen Zhao ◽  
Brian Paciotti ◽  
...  
Keyword(s):  
End Of Life ◽  
Rapid Development ◽  
Performance Status ◽  
Stage Iv ◽  
Prognostic Models ◽  
Time Period ◽  
Anti Cancer ◽  
Stage Iv Disease ◽  
And Performance ◽  
Record Review

229 Background: In 2001, after three months of review, the FDA approved the oral anticancer agent imatinib, making it the fastest approval in FDA history. Since then, the FDA has approved over 40 oral anti-cancer medications (OAMs) and the number continues to rise, transforming cancer care, improving survival in specific cancers and providing new hope. However, the rapid development of OAMs has produced uncertainty over the best use of these new medications, particularly at the end of life. ASCO guidelines recommend against prescribing intravenous chemotherapy within two weeks of expected death, but no such guidelines have yet been developed for OAMs. We describe one institution’s experience in prescribing OAMs at the end of life. Methods: An interdisciplinary team of pharmacy, oncology and palliative care specialists undertook an IRB-approved retrospective electronic health record review of patients who died between 1/1/2012 and 12/31/2015 and had been on one of seven oral anti-cancer medications (erlotinib, sunitinib, pazopanib, crizotinib, sorafenib, afatinib, regorafenib). From this cohort, descriptors such as diagnosis, stage, prior lines of therapy, ECOG, BMI and albumin were extracted. Results: There were at total of 62 patients who were on at least one of the seven drugs and died during the specified time period. Of these 62 patients, only 2 (3%) had a first prescription for an OAM in the last 30 days of life. Over 90% of the patients that were not prescribed an OAM within 30 days of death were patients with Stage IV disease with a median age of 66 and had an average of 3 prior lines of therapy. Consistent with prognostic models, these patients all had declining albumin, BMI and performance status. Conclusions: Oncologists at this institution rely on prognostic data to gauge when to recommend stopping IV chemotherapy before the last two weeks of life. Extrapolating from ASCO guidelines on the use of IV chemotherapy, these oncologists generally refrain from prescribing OAMs in the last 30 days of life. Unless strong data shows definitive benefit for the use of OAMs, we propose ASCO guidelines recommend not using OAMs during the last two weeks of life.

Image quality and radiation dose of CT venography with double dose reduction using model based iterative reconstruction: comparison with conventional CT venography using filtered back projection

2017 ◽  
Vol 59 (5) ◽  
pp. 546-552 ◽  
Author(s):  
Yeo-Jin Jeong ◽  
Ki Seok Choo ◽  
Kyung Jin Nam ◽  
Ji Won Lee ◽  
Jin You Kim ◽  
...  
Keyword(s):  
Image Quality ◽  
Radiation Dose ◽  
Iterative Reconstruction ◽  
Radiation Doses ◽  
Back Projection ◽  
Filtered Back Projection ◽  
Ct Venography ◽  
Group A ◽  
Vascular Enhancement ◽  
Group B

Background Computed tomography venography (CTV) at low kVp using model-based iterative reconstruction (MBIR) can enhance vascular enhancement with noise reduction. Purpose To evaluate image qualities and radiation doses of CTV at 80 kVp using MBIR and a small iodine contrast media (CM) dose and to compare these with those of CTV performed using a conventional protocol. Material and Methods Sixty-five patients (mean age = 58.1 ± 7.2 years) that underwent CTV for the evaluation of deep vein thrombosis (DVT) and varicose veins were enrolled in this study. Patients were divided into two groups: Group A (35 patients, 80 kVp, MBIR, automatic tube current modulation, CM = 270 mg/mL, 100 mL) and Group B (30 patients, 100 kVp, filtered back projection [FBP], 120 fixed mA, CM = 370 mg/mL, 120 mL). Objective and subjective image qualities of inferior vena cava (IVC), femoral vein (FV), and popliteal vein (PV) were assessed and radiation doses were recorded. Results Mean vascular enhancement in group A was significantly lower than in group B ( P < 0.01). Noise in group A was significantly lower than in group B except for PV and contrast-to-noise ratio were not significantly different in the two groups ( P > 0.05). In addition, radiation dose in group A was significantly lower than in group B ( P < 0.001). Subjective image quality comparison revealed group A was statistically inferior to group B except for subjective image noise. Conclusion CTV at 80 kVp using MBIR with small iodine contrast dose provided acceptable image quality at a lower radiation dose than conventional CTV using FBP.

Two Masterpieces of Kūṭiyāṭṭam

2019 ◽  
Keyword(s):  
Performance Studies ◽  
Empty Space ◽  
Ritual Studies ◽  
Indian Culture ◽  
Art Form ◽  
South Indian ◽  
Hebrew University ◽  
And Performance ◽  
The University

Kūṭiyāṭṭam, India’s only living traditional Sanskrit theatre, has been continually performed in Kerala for at least a thousand years. The actors and drummers create an entire world in the empty space of the stage by using spectacular costumes and make-up and by an immensely rich interplay of words, rhythms, mime, and gestures. This volume focuses on Mantrāṅkam and Aṅgulīyāṅkam, the two great masterpieces of Kūṭiyāṭṭam. It provides fundamental general remarks and relates them to pan-Indian reflections on aesthetics, philology, ritual studies, and history. Authored by scholars and active Kūṭiyāṭṭam performers, this is the first attempt to bring together a set of sustained, multi-faceted interpretations of these masterpieces-in-performance. With an aim to open up this ancient art form to readers interested in South Indian culture, religion, theatre and performance studies, philology, as well as literature, this volume offers a new way to access a major art form of pre-modern and modern Kerala. The University of Tuebingen in Germany and the Hebrew University of Jerusalem in Israel were partners in a long-term project studying and documenting Kūṭiyāṭṭam performances, including initiating full-scale performances of major works in the classical repertoire. We have been, in particular, focusing on the study of the two major, complex and ancient works, Mantrāṅkam and Aṅgulīyāṅkam, both of which we have seen and recorded in full. The articles in this volume are one of the results. They are supplemented with video-clips of lecture demonstrations provided online.

Cognitive Function in Children With Idiopathic Subclinical Hypothyroidism: Effects of 2 Years of Levothyroxine Therapy

2020 ◽  
Vol 105 (3) ◽  
pp. e774-e781 ◽  
Author(s):  
Donatella Capalbo ◽  
Sara Alfano ◽  
Miriam Polizzi ◽  
Raffaella Di Mase ◽  
Nicola Improda ◽  
...  
Keyword(s):  
Subclinical Hypothyroidism ◽  
Therapy Group ◽  
Cognitive Domains ◽  
Group A ◽  
Iq Scores ◽  
And Performance ◽  
Group B ◽  
Control Prospective Study

Abstract Background Long-term consequences of mild subclinical hypothyroidism (SH) in children are still unclear, and the need for levothyroxine (L-T4) supplementation remains controversial. We designed a 2-year, case-control, prospective study of a cohort of children with SH to evaluate the effects of L-T4 therapy on neurocognitive outcome. Methods Thirty-four children, age 9.1 ± 2.6 years, with long-lasting, idiopathic, and mild SH, and 34 healthy matched controls, were enrolled. Twenty SH children underwent a 2-year L-T4 treatment (group A), whereas 14 refused treatment and were reevaluated after a 2-year-follow-up (group B). IQ and specific cognitive domains were evaluated in all children at study entry and after 2 years of therapy (group A) or observation (group B) in SH individuals. Results In SH children baseline IQ scores were normal and comparable to controls (full-scale IQ [FSIQ] 100.4 ± 11.3 vs 101.8 ± 14.2, verbal IQ [VIQ] 99.7 ± 13.7 vs 98.3 ± 14.9 and performance IQ [PIQ] 101.2 ± 10.4 vs 105 ± 10.4). In group A, L-T4 treatment was associated with normalization of thyrotropin (6.3 ± 1.0 mIU/L at baseline vs 2.8 ± 1.4 mIU/L at 2 years, P &lt; .001). However, 2-year L-T4 therapy was not associated with a change in IQ scores (FSIQ 104.4 ± 13.8 vs 102.7 ± 11.0; VIQ 101.8 ± 14.9 vs 102.3 ± 11.9; and PIQ 106.5 ± 13.9 vs 102.7 ± 10.7) or in verbal or performance subtest scores. No significant differences were found in IQ scores after 2 years of treatment in group A compared to group B after a 2-year follow-up. Conclusions Our data suggest neurocognitive function in children is not impaired by persistent, mild, untreated SH and is not significantly modified by 2-year L-T4 supplementation.

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