scholarly journals Distinct Phenotypic Clusters of Glioblastoma Growth and Response Kinetics Predict Survival

2018 ◽  
pp. 1-14 ◽  
Author(s):  
Corbin A. Rayfield ◽  
Fillan Grady ◽  
Gustavo De Leon ◽  
Russell Rockne ◽  
Eduardo Carrasco ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Adjuvant Chemotherapy ◽  
Tumor Growth ◽  
Standard Of Care ◽  
Discrete Groups ◽  
Radial Expansion ◽  
Survival Difference ◽  
Significant Survival ◽  
Two Populations

Purpose Despite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype—growth before treatment and during each treatment to recurrence —has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK. Patients and Methods From our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment. Results There was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%). Conclusion Dichotomizing the heterogeneity of GBMs into two populations—one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival—suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.

scholarly journals Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

2011 ◽  
Vol 29 (34) ◽  
pp. 4491-4497 ◽  
Author(s):  
Edith A. Perez ◽  
Vera J. Suman ◽  
Nancy E. Davidson ◽  
Julie R. Gralow ◽  
Peter A. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
P Value ◽  
Sequential Administration ◽  
Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

Results of POUT: A phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 407-407 ◽  
Author(s):  
Alison Jane Birtle ◽  
John David Chester ◽  
Robert Jones Jones ◽  
Mark Johnson ◽  
Michaela Hill ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Randomised Trial ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Stopping Rules ◽  
Phase Iii ◽  
Early Stopping ◽  
Cross Sectional ◽  
Free Survival

407 Background: The role of post nephro-ureterectomy (NU) treatment for UTUC is unclear. POUT (CRUK/11/027; NCT01993979) addresses whether adjuvant chemotherapy improves disease free survival (DFS) for pts with histologically confirmed pT2-T4 N0-3 M0 UTUC. Methods: Pts (max n = 345) ≤90 days post NU were randomised (1:1) to 4 cycles of gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30-49ml/min) or surveillance with subsequent chemotherapy if required. Pts had 6 monthly cross sectional imaging and cystoscopy for the first 2 years, then annually to 5 years. Toxicity was assessed by CTCAE v4. Primary endpoint was DFS. The trial was powered to detect a hazard ratio (HR) of 0.65 (i.e. improvement in 3 year DFS from 40% to 55%; 2-sided alpha = 5%, 80% power) with Peto-Haybittle (p < 0.001) early stopping rules for efficacy & inefficacy. Secondary endpoints included metastasis-free survival (PFS), overall survival (OS), toxicity & quality of life. Results: Between May 2012 & Sept 2017, 248 pts were recruited (123 surveillance; 125 chemotherapy) at 57 UK centres. In Oct 2017, the independent trial oversight committees recommended POUT close to recruitment as data collected thus far (data snapshot 05/09/2017) met the early stopping rule for efficacy. At the time of interim analysis, median follow-up was 17.6 months (IQR 7.5-33.6). Pts had median age 69 years (range 36-88), 30% pT2, 65% pT3; 91% pN0;. Grade ≥3 toxicities were reported in 60% chemotherapy pts & 24% surveillance pts. 47/123 (surveillance) & 29/125 (chemotherapy) DFS events were reported; unadjusted HR = 0.47 (95% CI: 0.29, 0.74) in favour of chemotherapy (log-rank p = 0.0009). Two year DFS was 51% for surveillance (95% CI: 39, 61) and 70% for chemotherapy (95% CI: 58, 79). PFS favoured chemotherapy: HR = 0.49 (95% CI: 0.30, 0.79, p = 0.003). Conclusions: Adjuvant chemotherapy improved PFS in UTUC. POUT is the largest randomised trial in this pt population; the trial was terminated early because of efficacy favouring the chemotherapy arm. Whilst follow up for OS continues, this should be considered a new standard of care in these patients. Clinical trial information: ISRCTN98387754.

Timing of adjuvant chemotherapy initiation and colon cancer survival.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 119-119
Author(s):  
Aaron Gehr ◽  
Yan Lu ◽  
Bassam Ghabach ◽  
Kalyani Narra ◽  
Latha Sri Neerukonda ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Cancer Diagnosis ◽  
Pragmatic Trial ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Survival Difference ◽  
National Quality

119 Background: The National Quality Forum endorsed initiation of adjuvant chemotherapy within 120 days of diagnosis for stage III colon cancer patients aged < 80 years. Nevertheless, no trials were conducted to establish this 120-day threshold and observational studies used to justify this threshold may be sensitive to recently identified sources of bias. Therefore, we aimed to assess the effect of initiating adjuvant chemotherapy within 120 days on survival among patients with stage III colon cancer. Methods: We used institutional registry data from the JPS Center for Cancer Care (JPS), an accredited Comprehensive Community Cancer Program. Eligible patients were adults aged < 80 years, diagnosed with first primary stage III colon cancer between 2011 and 2015, and received at least part of their first course treatment at JPS. Overall survival was defined as time from cancer diagnosis to death, loss to follow-up, or end of study. We emulated a pragmatic trial and estimated the intention to treat 36-month restricted mean survival difference and 95% confidence limits (CL) for initiating adjuvant chemotherapy within 120 days using a marginal structural model with stabilized inverse probability of treatment weights to reduce confounding bias. Results: Our study population comprised 62 patients, of whom 61% were aged 55 – 64 years, 58% were females, 61% were racial/ethnic minorities, 69% were uninsured, and 61% initiated adjuvant chemotherapy within 120 days after cancer diagnosis. The mean survival after 36 months of follow-up was 31 months (95% CL: 27, 34) for patients who initiated and 31 months (95% CL: 28, 34) for patients who did not initiate adjuvant chemotherapy within 120 days (mean survival difference = -0.10 months, 95% CL: -3.6, 3.4). Conclusions: Our results suggest no meaningful difference in overall survival between initiating or not initiating adjuvant treatment within 120 days of diagnosis for patients with stage III colon cancer, but our estimates are compatible with either a 3-month survival benefit or harm. A larger sample size may provide greater certainty whether the 120-day threshold is a questionable quality measure, as observed in our study.

scholarly journals Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up

2018 ◽  
Vol 5 ◽  
Author(s):  
Ahmed M. A. Elsakka ◽  
Mohamed Abdel Bary ◽  
Eman Abdelzaher ◽  
Mostafa Elnaggar ◽  
Miriam Kalamian ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Standard Of Care ◽  
Metabolic Therapy

scholarly journals Prognostic factors and outcomes in anaplastic gliomas: An institutional experience

2018 ◽  
Vol 07 (01) ◽  
pp. 01-04 ◽  
Author(s):  
Deepthi Valiyaveettil ◽  
Monica Malik ◽  
Deepa Joseph ◽  
Syed Fayaz Ahmed ◽  
Syed Akram Kothwal
Keyword(s):  
Adjuvant Chemotherapy ◽  
Treatment Guidelines ◽  
Standard Of Care ◽  
Adjuvant Radiation ◽  
Karnofsky Performance Score ◽  
Focal Neurological Deficit ◽  
Time To Recurrence ◽  
Anaplastic Gliomas ◽  
Institutional Experience

Abstract Background: There is lack of clear evidence and treatment guidelines for anaplastic gliomas (AGs) with very few studies focusing exclusively on these patients. The aim of the study was to analyze the clinical profile and survival in these patients. Materials and Methods: Patients of AGs treated with radiation and concurrent ± adjuvant chemotherapy from January 2010 to December 2015 were analyzed. Statistical analysis was done using SPSS version 20 software. Results: A total of 100 patients were included in the study. The median age was 35 years (range 6–68 years). Eighty-four patients had follow-up details and were included for survival analysis. The 5-year overall survival (OS) was 58%. Age, presentation with seizures, and focal neurological deficit were not found to significantly influence survival. The 5-year survival for oligodendroglioma and astrocytoma was 69% and 52%, respectively. Patients with Karnofsky Performance Score (KPS) of ≥70 had a significantly better 5-year OS (65%) as compared to those with KPS <70 (33%) (P = 0.000). The use of adjuvant temozolomide (TMZ) showed longer 5-year OS of 67.7% compared to 36% in patients who did not receive adjuvant chemotherapy (P = 0.018). Patients receiving both concurrent and adjuvant TMZ showed longer 5-year OS (68.5% vs. 40%, P = 0.010). Twenty-two patients had recurrence with average time to recurrence being 37 months. Fourteen patients underwent salvage surgery and two patients received reirradiation. Conclusions: OS significantly correlated with KPS and receipt of concurrent and adjuvant chemotherapy with TMZ. Therefore, adjuvant radiation with concurrent and adjuvant TMZ should be the standard of care for AGs.

Long-term follow-up (>20 years) for one of the original randomized prospective trials evaluating adjuvant chemotherapy in patients with high-grade operable osteosarcoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10514-10514
Author(s):  
W. D. Tap ◽  
F. R. Eilber ◽  
G. Rosen ◽  
J. Eckardt ◽  
A. Schwartz ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Expectant Management ◽  
Salvage Chemotherapy ◽  
High Grade ◽  
Doxorubicin Hydrochloride ◽  
Metastatic Osteosarcoma ◽  
Significant Survival ◽  
Long Term Follow Up

10514 Background: Neoadjuvant and adjuvant chemotherapy is now standard practice for patients who present with localized osteosarcoma. We present the long-term follow-up (>20years) for one of the original prospective randomized trials that compared adjuvant chemotherapy to no treatment in patients with high-grade operable osteosarcoma. Methods: The original study was performed at UCLA from 1981 to 1984. During this time, 59 patients with high-grade, operable, non-metastatic osteosarcoma were randomized to receive adjuvant chemotherapy (MSKCC T-10B protocol)(N=32; 24 men, 8 women, median age 15 yrs) vs. expectant management (N=27; 20 men, 7 women, median age 18 yrs). All patients received one neoadjuvant course of intra-arterial doxorubicin hydrochloride (90mg) and radiation (1750cGy). At a median follow-up of 2 years, there was a statistically significant improvement in both disease-free (55% vs. 20%, p<.01) and overall survival (80% vs. 48%, p<.01) for those who received immediate adjuvant chemotherapy. Upon recurrence, patients in the T-10B arm received salvage chemotherapy with doxorubicin hydrochloride and cisplatin while those in the expectant arm received the T-10B protocol. 27 years after the initiation of the trial, long-term follow-up was obtained on all patients. Results: Median follow-up time for survivors was 24 years. 18 patients in the adjuvant chemotherapy arm died of disease (DOD) while 14 have no evidence of disease (NED). 22 patients in the control arm DOD, 1 died of other causes and 4 have NED. The 5, 10, and 20 year disease specific survival (DSS) for the treatment arm (47%, 43%, 43% respectfully) was significantly better than that of the control arm (30%, 26%, 17% respectfully) (p=0.0254). Conclusions: Early administration of chemotherapy in patients with high-grade operable osteosarcoma provides a significant survival benefit that is maintained with long-term (>20 years) follow-up. These results support the idea that early systemic treatment offers the best opportunity to cure patients with this high-risk malignancy. No significant financial relationships to disclose.

Retrospective analysis of stage IIIc uterine carcinoma patients: A single center experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15572-e15572
Author(s):  
Selim Yalcin ◽  
Samed Rahatli ◽  
Nadire Kucukoztas ◽  
Ozlem Ozen ◽  
Nihan Haberal ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Chemotherapy ◽  
Clear Cell ◽  
Standard Of Care ◽  
Undifferentiated Carcinoma ◽  
Serous Carcinoma ◽  
Current Standard ◽  
Stage Iiic ◽  
Single Center Experience

e15572 Background: Stage IIIC comprises 8% of all endometrial cancers. Both local and systemic relapse risks are high. Current standard of care is adjuvant chemotherapy; however the addition of radiotherapy seems to improve outcomes in retrospective series but prospective data is lacking. We herein report outcomes of our patients with stage IIIC endometrial cancer operated and treated with adjuvant chemotherapy±radiotherapy. Methods: 29 patients with stage IIIC endometrial cancer diagnosed between 2006-2011 were included. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of DFS and OS were analyzed. Results: Median age was 64 (41-82). Surgical procedure was TAH+BSO+BPPLND and omentectomy in 26 patients. 4 patients who were operated (TAH+BSO) in another center were restaged and BPPLND and omentectomy were performed. 13 patients (45%) had endometrioid histology, 11 (38%) had papillary serous carcinoma, 2 (7%) had clear cell carcinoma, 2 (7%) had mixed carcinoma and 1 (3%) had undifferentiated carcinoma. 6 patients had ovarian, 9 had uterine serosal involvement, 1 had positive cytology of abdominal washing, 18 (62%) had lymph node-only disease. 14 patients (48%) had positive nodes both in pelvic and paraaortic region, 9 (31%) only in pelvic region and 6 (21%) only in paraaortic region. 24 patients (83%) received chemotherapy with paclitaxel and carboplatin, 13 (45%) received external RT, 4 (14%) received brachytherapy and 3 (10%) patients received chemoradiation with weekly cisplatin or carboplatin. Median follow-up was 19 months. 10 patients recurred during follow-up and 6 patients died. All of the recurrences except one were intraabdominal. 3-year PFS was 64% and OS was 71.6%. Conclusions: With the use contemporary chemotherapy regimens and radiotherapy, we achieved ~70% 3-year survival rate in stage IIIC endometrial carcinoma patients with 45% of the patients having high risk histologies (serous and clear cell). We propose that combined adjuvant chemotherapy and radiation might improve survival in patients with advanced stage disease compared to either modality alone. Results of GOG258 and PORTEC 3 trials should be awaited for definitive conclusions.

scholarly journals Testing telediagnostic thyroid ultrasound in Peru: a new horizon in expanding access to imaging in rural and underserved areas

2021 ◽  
Author(s):  
T. J. Marini ◽  
S. L. Weiss ◽  
A. Gupta ◽  
Y. T. Zhao ◽  
T. M. Baran ◽  
...  
Keyword(s):  
Thyroid Nodule ◽  
Standard Of Care ◽  
The United States ◽  
Epidemiological Studies ◽  
Thyroid Ultrasound ◽  
Target Region ◽  
Experienced Radiologist ◽  
Significant Difference ◽  
Size Evaluation

Abstract Purpose Thyroid ultrasound is a key tool in the evaluation of the thyroid, but billions of people around the world lack access to ultrasound imaging. In this study, we tested an asynchronous telediagnostic ultrasound system operated by individuals without prior ultrasound training which may be used to effectively evaluate the thyroid and improve access to imaging worldwide. Methods The telediagnostic system in this study utilizes volume sweep imaging (VSI), an imaging technique in which the operator scans the target region with simple sweeps of the ultrasound probe based on external body landmarks. Sweeps are recorded and saved as video clips for later interpretation by an expert. Two operators without prior ultrasound experience underwent 8 h of training on the thyroid VSI protocol and the operation of the telemedicine platform. After training, the operators scanned patients at a health center in Lima. Telediagnostic examinations were sent to the United States for remote interpretation. Standard of care thyroid ultrasound was performed by an experienced radiologist at the time of VSI examination to serve as a reference standard. Results Novice operators scanned 121 subjects with the thyroid VSI protocol. Of these exams, 88% were rated of excellent image quality showing complete or near complete thyroid visualization. There was 98.3% agreement on thyroid nodule presence between VSI teleultrasound and standard of care ultrasound (Cohen’s kappa 0.91, P < 0.0001). VSI measured the thyroid size, on average, within 5 mm compared to standard of care. Readers of VSI were also able to effectively characterize thyroid nodules, and there was no significant difference in measurement of thyroid nodule size (P = 0.74) between VSI and standard of care. Conclusion Thyroid VSI telediagnostic ultrasound demonstrated both excellent visualization of the thyroid gland and agreement with standard of care thyroid ultrasound for nodules and thyroid size evaluation. This system could be deployed for evaluation of palpable thyroid abnormalities, nodule follow-up, and epidemiological studies to promote global health and improve the availability of diagnostic imaging in underserved communities.

scholarly journals Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 324
Author(s):  
Jacob P. Fisher ◽  
David C. Adamson
Keyword(s):  
Controlled Trial ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Significant Survival ◽  
One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

scholarly journals Evaluation of adherence monitoring system using evriMED with a differentiated response compared to standard of care among drug-sensitive TB patients in three provinces in South Africa: a protocol for a cluster randomised control trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Noriah Maraba ◽  
Catherine Orrell ◽  
Candice M. Chetty-Makkan ◽  
Kavindhran Velen ◽  
Rachel Mukora ◽  
...  
Keyword(s):  
South Africa ◽  
Treatment Success ◽  
Standard Of Care ◽  
Treatment Completion ◽  
Phone Call ◽  
Randomised Control Trial ◽  
Improve Medication Adherence ◽  
Tb Treatment ◽  
Differentiated Care

Abstract Background South Africa has achieved drug-susceptible TB (DS-TB) treatment success of only 77% among people with new and previously treated TB. Alternative approaches are required to improve medication adherence and treatment completion to limit transmission, TB relapse and the development of resistance. This study aims to implement and evaluate the use of adherence medication monitors (Wisepill evriMED 1000) with a differentiated response to patient care, among DS-TB patients in three provinces of South Africa. Methods In total, 18 public health clinics across three provinces were selected. Clinics were randomised to intervention or standard of care clinics. In each clinic, approximately 145 DS-TB patients are being enrolled to reach a total of 2610. All patients have their daily adherence monitored using medication monitors. In the intervention arm, patients are receiving medication monitor reminders and differentiated care in response to adherence data. This weekly review of daily real-time monitoring will be undertaken from a central database. The differentiated care model includes automated SMS reminders with a missed dose, research staff-initiated phone call to the patient with a second or third missed dose, a home visit if four or more doses are missed, and motivational counselling if four or more doses are missed repeatedly. Fidelity of the intervention will be measured through process evaluation. Patients in control clinics will receive medication monitors for adherence tracking, standard of care TB education, and normal clinic follow-up procedures. The primary outcome is the proportion of patients by arm with >80% adherence, as measured by the medication monitor. The feasibility and acceptability of the intervention will be assessed by in-depth interviews with patients, stakeholders, and study staff. A cost effectiveness analysis of the intervention and standard of care clinics will be conducted. Significance This trial will provide evidence for the use of an intervention, including medication monitors and differentiated care package, to improve adherence to TB treatment. Improved adherence should also improve TB treatment completion rates, thus reducing loss to follow-up rates, and TB relapse among people with TB. The intervention is intended to ultimately improve overall TB control and reduce TB transmission in South Africa. Trial registration Pan African Trial Registry PACTR201902681157721. Registered on 11 February 2019.

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