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1.
J Neurooncol ; 164(1): 1-9, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37493865

ABSTRACT

PURPOSE: Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. METHODS: We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method. RESULTS: Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53-0.75; p < 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6-41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4-21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (p < 0.001). CONCLUSIONS: Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.


Subject(s)
Brain Neoplasms , Electric Stimulation Therapy , Glioblastoma , Humans , Glioblastoma/pathology , Temozolomide/therapeutic use , Electric Stimulation Therapy/methods , Brain Neoplasms/pathology , Combined Modality Therapy
2.
Curr Oncol ; 30(6): 5195-5200, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37366877

ABSTRACT

(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6-649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9-21.6 h), representing 50% (range: 8-90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1-17 h), representing 38% (range: 13-71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.


Subject(s)
Mesothelioma, Malignant , Neoplasms , Humans
3.
JAMA Netw Open ; 6(5): e2312824, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37166798

ABSTRACT

Importance: Patients with recurrent or unresectable skin cancers have limited treatment options. Diffusing alpha-emitter radiation therapy (DaRT), a novel solid tumor management strategy using alpha-particle interstitial brachytherapy, may address this challenge. Objective: To evaluate the feasibility and safety of using DaRT to manage recurrent or unresectable skin cancers. Design, Setting, and Participants: This prospective cohort study of patients who received a 2-week to 3-week treatment course and were followed up for 24 weeks after treatment during 2021 and 2022 at 2 sites in the US. Patients with malignant skin tumors or soft tissue tumors were recruited if they had limited treatment options for tumors recurrent after prior surgery or external beam radiotherapy or unresectable tumors. Intervention: Patients underwent DaRT to deliver a physical dose of 10 Gy (equivalent weighted dose of 200 CGE) to the tumor. Main Outcomes and Measures: Feasibility of the DaRT procedure was evaluated based on the ability of investigators to successfully deliver radiation to the tumor. Patients were followed up for adverse events (AEs) for 24 weeks and for tumor response by physicians' physical examination and imaging 12 weeks after device removal. Results: This study included 10 participants with recurrent or unresectable skin cancer (median [IQR] age, 72 [68-75] years; 6 males [60%]; 4 females [40%]). Six patients (60%) had recurrent disease, and 4 (40%) had tumors that were deemed unresectable. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. Median (range) tumor volume before treatment was 2.1 cm3 (0.65-12.65 cm3). The mean (SD) prescription dose coverage of the gross tumor volume was 91% (2.8%) with all tumors having coverage of 85% or more. No device-related grade 3 AEs were noted. Common AEs were grade 1 to 2 erythema, edema, and pruritus. At 12 weeks following treatment, there was a 100% complete response rate. Nine of 10 complete responses (90%) were confirmed by CT imaging. Conclusions and Relevance: This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers. The favorable safety profile and high response rates are promising. A US trial for marketing approval based on this pilot study is under way. Trial Registration: ClinicalTrials.gov Identifier: NCT04377360.


Subject(s)
Brachytherapy , Skin Neoplasms , Male , Female , Humans , Aged , Brachytherapy/adverse effects , Cohort Studies , Prospective Studies , Pilot Projects , Feasibility Studies , Skin Neoplasms/radiotherapy
4.
J Geriatr Oncol ; 14(1): 101393, 2023 01.
Article in English | MEDLINE | ID: mdl-36692964

ABSTRACT

INTRODUCTION: Cancer remains a substantial burden on society. Our objective was to update projections on the number of new cancer diagnoses in the United States by age, race, ethnicity, and sex through 2040. MATERIALS AND METHODS: Population-based cancer incidence data were obtained using Surveillance, Epidemiology, and End Results (SEER) data. Population estimates were made using the 2010 US Census data population projections to calculate future cancer incidence. Trends in age-adjusted incidence rates for 23 cancer types along with total cancers were calculated and incorporated into a second projection model. RESULTS: If cancer incidence remains stable, annual cancer diagnoses are projected to increase by 29.5% from 1.86 million to 2.4 million between 2020 and 2040. This increase outpaces the projected US population growth of 12.3% over the same period. The population of older adults is projected to represent an increasing proportion of total cancer diagnoses with patients ≥65 years old comprising 69% of all new cancer diagnoses and patients ≥85 years old representing 13% of new diagnoses by 2040. Cancer diagnoses are projected to increase in racial minority groups, with a projected 44% increase in Black Americans (from 222,000 to 320,000 annually), and 86% in Hispanic Americans (from 175,000 to 326,000 annually). DISCUSSION: The landscape of cancer care will continue to change over the next several decades. The burden of disease will remain substantial, and the growing proportion of older and minority patients with cancer remains of particular interest. These projections should help guide future health policy and research priorities.


Subject(s)
Ethnicity , Neoplasms , Humans , United States , Aged , Aged, 80 and over , Incidence , Neoplasms/epidemiology , Black or African American , Forecasting
5.
Neurooncol Adv ; 4(1): vdac150, 2022.
Article in English | MEDLINE | ID: mdl-36249289

ABSTRACT

Background: Determinates of tumor treating fields (TTFields) usage in patients receiving combined modality therapy for primary IDH wild-type glioblastoma are currently unknown. Methods: Ninety-one patients underwent maximal debulking surgical resection, completed external beam radiotherapy with concurrent Temozolomide (TMZ), and initiated adjuvant TMZ with or without TTFields. We performed a retrospective analysis of patient, tumor, and treatment-related factors that affected TTFields usage. Results: We identified three TTFields usage subgroups: 32 patients that declined TTFields, 40 patients that started, but had monthly compliance of less than 75% or used it for less than 2 months, and 19 patients who used TTFields for 2 or more months and maintained average monthly compliance greater than 75%. With 26.5 months median follow-up for surviving patients, the 1- and 3-year actuarial overall survival for all patients was 80% and 18%, respectively. On multivariate analysis TTFields use (P = .03), extent of surgical resection (P = 0.02), and MGMT methylation status (P = .01) were significantly associated with overall survival. TTFields usage was explored as a continuous variable and higher average usage was associated with longer overall survival (P = .03). There was no relationship between patient, tumor, or treatment-related factors and a patient's decision to use TTFields. Conclusions: No subgroup of patients was more or less likely to initiate TTFields therapy and no subgroup was more or less likely to use TTFields as prescribed. The degree of TTFields compliance may be associated with improved survival independent of other factors.

6.
Int J Radiat Oncol Biol Phys ; 112(5): 1269-1278, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34963556

ABSTRACT

PURPOSE: Tumor-treating fields (TTFields) are an antimitotic treatment modality that interfere with glioblastoma (GBM) cell division and organelle assembly by delivering low-intensity, alternating electric fields to the tumor. A previous analysis from the pivotal EF-14 trial demonstrated a clear correlation between TTFields dose density at the tumor bed and survival in patients treated with TTFields. This study tests the hypothesis that the antimitotic effects of TTFields result in measurable changes in the location and patterns of progression of newly diagnosed GBM. METHODS AND MATERIALS: Magnetic resonance images of 428 newly diagnosed GBM patients who participated in the pivotal EF-14 trial were reviewed, and the rates at which distant progression occurred in the TTFields treatment and control arm were compared. Realistic head models of 252 TTFields-treated patients were created, and TTFields intensity distributions were calculated using a finite element method. The TTFields dose was calculated within regions of the tumor bed and normal brain, and its relationship with progression was determined. RESULTS: Distant progression was frequently observed in the TTFields-treated arm, and distant lesions in the TTFields-treated arm appeared at greater distances from the primary lesion than in the control arm. Distant progression correlated with improved clinical outcome in the TTFields patients, with no such correlation observed in the controls. Areas of normal brain that remained normal were exposed to higher TTFields doses compared with normal brain that subsequently exhibited neoplastic progression. Additionally, the average dose to areas of the enhancing tumor that returned to normal was significantly higher than in the areas of the normal brain that progressed to enhancing tumor. CONCLUSIONS: There was a direct correlation between TTFields dose distribution and tumor response, confirming the therapeutic activity of TTFields and the rationale for optimizing array placement to maximize the TTFields dose in areas at highest risk of progression, as well as array layout adaptation after progression.


Subject(s)
Antimitotic Agents , Brain Neoplasms , Electric Stimulation Therapy , Glioblastoma , Antimitotic Agents/therapeutic use , Brain/diagnostic imaging , Brain/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Electric Stimulation Therapy/methods , Glioblastoma/diagnostic imaging , Glioblastoma/radiotherapy , Humans , Magnetic Resonance Imaging
8.
J Am Acad Dermatol ; 85(3): 539-548, 2021 09.
Article in English | MEDLINE | ID: mdl-34116097

ABSTRACT

Radiation therapy offers distinct advantages over other currently available treatments for cutaneous malignancies in certain circumstances. Dermatologists and dermatologic surgeons should be familiar with the available radiation therapy techniques as well as their value and potential limitations in a variety of clinical scenarios. The first article in this 2-part continuing medical education series highlights the mechanisms, modalities, and applications of the most commonly used radiotherapy treatments as they relate to cutaneous oncology. We review the current indications for the use of radiation in the treatment of various cutaneous malignancies, the techniques commonly employed in modern radiotherapy, and the associated complications.


Subject(s)
Brachytherapy , Skin Neoplasms , Humans , Radiotherapy/adverse effects , Skin Neoplasms/radiotherapy
9.
J Am Acad Dermatol ; 85(3): 551-562, 2021 09.
Article in English | MEDLINE | ID: mdl-34116100

ABSTRACT

Radiation therapy may be performed for a variety of cutaneous malignancies, depending on patient health status, tumor clinical and histologic features, patient preference, and resource availability. Dermatologists should be able to recognize the clinical scenarios in which radiation therapy is appropriate, as this may reduce morbidity, decrease risk of disease recurrence, and improve quality of life. The second article in this 2-part continuing medical education series focuses on the most common indications for radiation therapy in the treatment of basal cell carcinoma, cutaneous squamous cell carcinoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi sarcoma, angiosarcoma, cutaneous lymphoma, melanoma, undifferentiated pleomorphic sarcoma, and sebaceous carcinoma.


Subject(s)
Carcinoma, Squamous Cell , Sarcoma , Sebaceous Gland Neoplasms , Skin Neoplasms , Carcinoma, Squamous Cell/radiotherapy , Humans , Neoplasm Recurrence, Local/radiotherapy , Quality of Life , Sarcoma/radiotherapy , Sebaceous Gland Neoplasms/radiotherapy , Skin Neoplasms/radiotherapy
10.
Ann Surg ; 274(6): e507-e514, 2021 12 01.
Article in English | MEDLINE | ID: mdl-31663972

ABSTRACT

BACKGROUNDS: To determine the potential survival benefit associated with robotic-assisted laparoscopic prostatectomy (RALP) compared to open radical prostatectomy (ORP) for prostate cancer. SUMMARY OF BACKGROUND DATA: RALP has become the dominant surgical approach for localized disease in the absence of randomized clinical evidence and despite of the factor that RALP is more expensive than ORP. METHODS: We performed a cohort study involving patients who underwent RALP and ORP for localized prostate cancer at the Commission on Cancer- accredited hospitals in the United States. Overall survival was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. An interrupted time-series analysis using the surveillance, epidemiology, and end results program database was also performed. RESULTS: From 2010 to 2011, 37,645 patients received RALP and 12,655 patients received ORP. At a median follow-up of 60.7 months, RALP was associated with improved overall survival by both univariate [hazard ratio (HR), 0.69; P < 0.001] and multivariate analysis (HR, 0.76; P < 0.001) compared with ORP. Propensity score-matched analysis demonstrated improved 5-year all-cause mortality (3.9% vs 5.5%, HR, 0.73; P < 0.001) for RALP. The interrupted time-series analysis demonstrated the adoption of robotic surgery coincided with a systematic improvement in the 5-year cancer-specific survival rate of 0.17% (95% confidence interval, 0.06-0.25) per year after 2003 (P = 0.004 for change of trend), as compared to the time before adoption of RALP (1998-2003, annual percentage change, 0.01%; 95% confidence interval, -0.06 to 0.08). Sensitivity analysis suggested that the results from the interrupted time-series analysis were consistent with the improvement in the all-cause mortality demonstrated in the survival analysis (P = 0.87). CONCLUSIONS: In this epidemiologic analysis, RALP was associated with a small but statistically significant improvement in 5-year all-cause mortality compared to ORP for localized prostate cancer. This is the first time in the literature to report a survival benefit with RALP. Our findings have significant quality and cost implications, and provide assurance regarding a dominant adoption of more expensive technology in the absence of randomized controlled trials.


Subject(s)
Laparoscopy/methods , Prostatectomy/methods , Prostatic Neoplasms/mortality , Prostatic Neoplasms/surgery , Robotic Surgical Procedures , Aged , Humans , Interrupted Time Series Analysis , Kaplan-Meier Estimate , Male , Middle Aged , Propensity Score , Proportional Hazards Models
11.
Front Oncol ; 10: 1045, 2020.
Article in English | MEDLINE | ID: mdl-32850308

ABSTRACT

Importance: Tumor Treating Fields (TTFields) are an anti-mitotic treatment approved for treating newly diagnosed and recurrent glioblastoma, and mesothelioma. TTFields in glioblastoma comprise alternating electric fields (200 kHz) delivered continuously, ideally for ≥18 h/day, to the tumor bed via transducer arrays placed on the shaved scalp. When applied locoregionally to the tumor bed and combined with systemic temozolomide chemotherapy, TTFields improved overall survival vs. temozolomide alone in patients with newly diagnosed glioblastoma. Improved efficacy outcomes with TTFields were demonstrated, while maintaining a well-tolerated and manageable safety profile. The most commonly-reported TTFields-associated adverse events (AEs) are beneath-array dermatologic events. Since survival benefit from TTFields increases with duration-of-use, prevention and management of skin AEs are critical to maximize adherence. This paper describes TTFields-associated dermatological AEs and recommends prevention and management strategies based on clinical trial evidence and real-world clinical experience. Observations: TTFields-associated skin reactions include contact dermatitis (irritant/allergic), hyperhidrosis, xerosis or pruritus, and more rarely, skin erosions/ulcers and infections. Skin AEs may be prevented through skin-care and shifting (~2 cm) of array position during changes. TTFields-related skin AE management should be based on clinical phenotype and severity. Depending on diagnosis, recommended treatments include antibiotics, skin barrier films, moisturizers, topical corticosteroids, and antiperspirants. Water-based lotions, soaps, foams, and solutions with minimal impact on electrical impedance are preferred with TTFields use over petroleum-based ointments, which increase impedance. Conclusions: Early identification, prophylactic measures, and symptomatic skin AE management help patients maximize TTFields usage, while maintaining quality-of-life and optimizing therapeutic benefit. Implications for practice: TTFields confer a survival benefit in patients with glioblastoma that correlates positively with duration of daily use. Skin events (rash) are the primary treatment-related AE that can limit duration of use. The recommendations described here will help healthcare professionals to recognize, prevent, and manage dermatologic AEs associated with TTFields treatment. These recommendations may improve cutaneous health and support adherence to therapy, both of which would maximize treatment outcomes.

12.
Ocul Oncol Pathol ; 5(5): 340-349, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31559245

ABSTRACT

BACKGROUND/AIMS: The aim of this study is to report the burden of ocular morbidity following iodine-125 episcleral plaque brachytherapy (EPBT) in the treatment of American Joint Committee on Cancer (AJCC) T4-staged posterior uveal melanoma (PUM). METHODS: Clinical records of patients with T4-staged PUM treated with 125I EPBT were analyzed for incidence of treatment failure and radiation-induced complications. RESULTS: Cumulative incidence of local treatment failure was 9% (95% CI 5-15%) at 5 years and was associated with decreased tumor height (HR = 0.78; p = 0.01). Cumulative incidence of enucleation at 5 years was 21% and was correlated with worsening baseline visual acuity (HR = 1.42; p = 0.05). Increasing patient age was associated with higher rates of vitreous hemorrhage (HR = 1.03; p = 0.02) and cataract surgery (HR = 1.05; p < 0.001). Increased tumor height was associated with higher rates of neovascular glaucoma (HR = 1.16; p = 0.03) and vitreous hemorrhage (HR = 1.23; p < 0.001). CONCLUSION: 125I EPBT is an effective treatment for T4-staged PUM and achieves high rates of local control. Treatment failure appears to be more common among minimally elevated tumors. Other causes of ocular morbidity were associated with increasing tumor height, patient age, and baseline visual acuity.

13.
Oncologist ; 24(12): e1426-e1436, 2019 12.
Article in English | MEDLINE | ID: mdl-31444292

ABSTRACT

Tumor-treating fields (TTFields) are a noninvasive antimitotic cancer treatment consisting of low-intensity alternating electric fields delivered to the tumor or tumor bed via externally applied transducer arrays. In multiple in vitro and in vivo cancer cell lines, TTFields therapy inhibits cell proliferation, disrupts cell division, interferes with cell migration and invasion, and reduces DNA repair. Human trials in patients with primary glioblastoma showed an improvement in overall survival, and trials in patients with unresectable malignant pleural mesothelioma showed favorable outcomes compared with historical control. This led to U.S. Food and Drug Administration approval in both clinical situations, paving the way for development of trials investigating TTFields in other malignancies. Although these trials are ongoing, the existing evidence suggests that TTFields have activity outside of neuro-oncology, and further study into the mechanism of action and clinical activity is required. In addition, because TTFields are a previously unrecognized antimitotic therapy with a unique mode of delivery, the oncological community must address obstacles to widespread patient and provider acceptance. TTFields will likely join surgery, systemic therapy, and radiation therapy as a component of multimodality management of patients with solid malignancies. IMPLICATIONS FOR PRACTICE: Tumor-treating fields (TTFields) exhibit a broad range of antitumor activities. Clinically, they improve overall survival for patients with newly diagnosed glioblastoma. The emergence of TTFields has changed the treatment regimen for glioblastoma. Clinicians need to understand the practical issues surrounding its use in the multidisciplinary management of patients with glioblastoma. With ongoing clinical trials, TTFields likely will become another treatment modality for solid malignancies.


Subject(s)
Combined Modality Therapy/methods , Neoplasms/therapy , Humans
14.
Int J Radiat Oncol Biol Phys ; 104(5): 1106-1113, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31026557

ABSTRACT

INTRODUCTION: Tumor Treating Fields (TTFields) are approved for glioblastoma based on improved overall survival (OS) and progression-free survival (PFS) in the phase 3 EF-14 trial of newly diagnosed glioblastoma. To test the hypothesis that increasing TTFields dose at the tumor site improves patient outcomes, we performed a simulation-based study investigating the association between TTFields dose and survival (OS and PFS) in patients treated with TTFields in EF-14. METHODS AND MATERIALS: EF-14 patient cases (N = 340) were included. Realistic head models were derived from T1-contrast images captured at baseline. The transducer array layout on each patient was obtained from EF-14 records; average compliance (fraction of time patient was on active treatment) and average electrical current delivered to the patient were derived from log files of the TTFields devices used by patients. TTFields intensity distributions and power densities were calculated using the finite element method. Local minimum dose density (LMiDD) was defined as the product of TTFields intensity, tissue-specific conductivities, and patient compliance. The average LMiDD within a tumor bed comprising the gross tumor volume and the 3-mm-wide peritumoral boundary zone was calculated. RESULTS: The median OS and PFS were significantly longer when the average LMiDD in the tumor bed was ≥0.77 mW/cm3: OS was 25.2 versus 20.4 months (P = .003, hazard ratio [HR] = 0.611) and PFS was 8.5 versus 6.7 months (P = .02, HR = 0.699). The median OS and PFS were longer when the average TTFields intensity was >1.06 V/cm: OS was 24.3 versus 21.6 months (P = .03, HR = 0.705) and PFS was 8.1 versus 7.9 months (P = .03, HR = 0.721). CONCLUSIONS: In this study we present the first reported analysis demonstrating patient-level dose responses to TTFields. We provide a rigorous definition for TTFields dose and set a conceptual framework for future work on TTFields dosimetry and treatment planning.


Subject(s)
Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Glioblastoma/mortality , Glioblastoma/radiotherapy , Adult , Aged , Aged, 80 and over , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Electrophysiological Phenomena , Female , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Progression-Free Survival , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Transducers , Young Adult
16.
J Natl Compr Canc Netw ; 17(1): 29-37, 2019 01.
Article in English | MEDLINE | ID: mdl-30659127

ABSTRACT

Background: Chemotherapy with or without pelvic radiotherapy (RT) is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for metastatic anal cancer (MAC), despite limited clinical evidence for RT in this setting. In addition, increasing evidence shows that local therapies, including RT, may increase patient survival for some types of metastatic cancers. The purpose of this study was to evaluate the patterns of care and association between definitive pelvic RT and overall survival (OS) for patients with MAC. Methods: The National Cancer Database was analyzed to evaluate OS of patients with newly diagnosed MAC treated with chemotherapy with or without pelvic RT. Those who did not undergo treatment, treated with surgery, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results: From 2004 through 2015, 437 patients received chemotherapy alone and 1,020 received pelvic chemoradiotherapy (CRT). At a median follow-up of 17.3 months, CRT was associated with improved OS on univariate (P<.001) and multivariate analysis (hazard ratio [HR], 0.70; 95% CI, 0.61-0.81; P<.001). Propensity score-matched analysis demonstrated superior median survival (21.3 vs 15.9 months) and 2-year OS rates (46% vs 34%) with CRT compared with chemotherapy alone (P<.001). Landmark analyses limited to long-term survivors of ≥1, ≥2, and ≥4 years showed improved OS with CRT in all subsets (all P<.05). CRT with therapeutic doses (≥45 Gy) was associated with longer median survival than palliative doses (<45 Gy) and chemotherapy alone (24.9 vs 10.9 vs 15.6 months, respectively; P<.001). The benefit of CRT was present among not only those with distant lymph node metastasis (HR, 0.63; P=.04) but also those with distant organ disease (HR, 0.74; P<.001). Conclusions: In this large hypothesis-generating analysis, patients with newly diagnosed MAC who received definitive pelvic RT with chemotherapy lived significantly longer than those who received chemotherapy alone. Prospective trials evaluating definitive local RT for MAC are warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/statistics & numerical data , Lymphatic Metastasis/therapy , Adult , Aged , Aged, 80 and over , Anus Neoplasms/mortality , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Chemoradiotherapy/methods , Chemoradiotherapy/standards , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Prospective Studies , Radiotherapy Dosage , Registries/statistics & numerical data , Survival Rate , Time Factors , Treatment Outcome , United States/epidemiology
17.
Pract Radiat Oncol ; 9(1): e4-e13, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30125673

ABSTRACT

PURPOSE: This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy. METHODS AND MATERIALS: A total of 281 patients with pTis, pT1N0, or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled from December 2008 through August 2014. APBI was delivered using 3-dimensional CRT (n = 29) or with SAVI (n = 176), Contura (n = 56), or MammoSite (n = 20) brachytherapy catheters. Patients were evaluated at protocol-specified intervals, at which time the radiation oncologist scored cosmetic outcome, toxicities, and recurrence status using a standardized template. RESULTS: The median follow-up time is 41 months. Grade 1 seroma and fibrosis were more common with brachytherapy than with 3-dimensional CRT (50.4% vs 3.4% for seroma; P < .0001 and 66.3% vs 44.8% for fibrosis; P = .02), but grade 1 edema was more common with 3-dimensional CRT than with brachytherapy (17.2% vs 5.6%; P = .04). Grade 2 to 3 pain was more common with 3-dimensional CRT (17.2% vs 5.2%; P = .03). Actuarial 5-year rates of fair or poor radiation oncologist-reported cosmetic outcome were 9% for 3-dimensional CRT and 24% for brachytherapy (P = .13). Brachytherapy was significantly associated with inferior cosmesis on mixed model analysis (P = .003). Significant predictors of reduced risk of adverse cosmetic outcome after brachytherapy were D0.1cc (skin) ≤102%, minimum skin distance >5.1 mm, dose homogeneity index >0.54, and volume of nonconformance ≤0.89 cc. The 5-year ipsilateral breast recurrence was 4.3% for brachytherapy and 4.2% for 3-dimensional CRT APBI patients (P = .95). CONCLUSIONS: Brachytherapy APBI is associated with higher rates of grade 1 fibrosis and seroma than 3-dimensional CRT but lower rates of grade 1 edema and grade 2 to 3 pain than 3-dimensional CRT. Rates of radiation oncologist-reported fair or poor cosmetic outcomes are higher with brachytherapy. We identified dosimetric parameters that predict reduced risk of adverse cosmetic outcome after brachytherapy-based APBI. Ipsilateral breast recurrence was equivalent for brachytherapy and 3-dimensional CRT.


Subject(s)
Brachytherapy/adverse effects , Breast Neoplasms/radiotherapy , Cosmetics , Neoplasm Recurrence, Local/diagnosis , Radiation Injuries/etiology , Radiotherapy, Intensity-Modulated/adverse effects , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Lobular/pathology , Carcinoma, Lobular/radiotherapy , Edema/etiology , Female , Fibrosis/etiology , Follow-Up Studies , Humans , Middle Aged , Pain/etiology , Prognosis , Prospective Studies , Radiotherapy Dosage , Seroma/etiology
19.
J Neurol Surg B Skull Base ; 78(3): 251-255, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28593112

ABSTRACT

Objective This case series investigates management of glomus jugulare (GJ) tumors utilizing definitive and salvage Gamma Knife stereotactic radiosurgery (GKSRS). Methods A retrospective chart review was performed to collect data. Statistical analysis included patient, tumor, and treatment information. Results From 1996 to 2013, 17 patients with GJ received GKSRS. Median age was 64 years (range, 27-76). GKSRS was delivered for definitive treatment in eight (47%) and salvage in nine (53%) patients. Median tumor volume was 9.8 cm 3 (range, 2.8-42 cm 3 ). Median dose was 15 Gy (range, 13-18 Gy). Median follow-up was 123 months (range, 38-238 months). Tumor size decreased in 10 (59%), stabilized in 6 (35%), and increased in 1 patient (6%). Overall neurological deficit improved in 53%, stabilized in 41%, and worsened in 6% of patients. Overall cause-specific survival was 100%, and actuarial local control was 94%. Eighty-eight percent of patients without prior resection experienced neurologic deficit improvement, while 25% of patients with prior resection experienced neurologic improvement ( p = 0.02). Conclusion Gamma Knife radiosurgery provides effective long-term control of GJ and overall improvement or stabilization of neurological deficit in most patients. Patients with prior resection are less likely to experience improvement of neurologic deficit.

20.
Am J Ophthalmol ; 176: 40-45, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28048976

ABSTRACT

PURPOSE: To report the outcomes of survival, local control, visual acuity, and eye retention in patients treated with repeat episcleral plaque brachytherapy (EPBT) for locally recurrent posterior uveal melanoma (PUM). DESIGN: Retrospective, interventional case series. METHODS: Setting: Institutional. PATIENT POPULATION: A total of 1201 patients that underwent iodine-125 (I-125) EPBT as primary treatment for PUM between 1985 and 2015. INCLUSION CRITERIA: Development of locally recurrent disease and retreatment with I-125 EPBT. OBSERVATION PROCEDURES: Clinical records review. MAIN OUTCOME MEASURES: Visual acuity, Kaplan-Meier estimates of survival, local control, metastasis, and loss of the eye over the duration of follow-up. RESULTS: Twenty-seven patients (13 men) met our inclusion criteria. Median (range) follow-up from initial treatment was 100 months (14-365 months), while median time to local recurrence was 43 months (9-185 months). Median (range) follow-up after retreatment was 47 months (3-120 months). Kaplan-Meier estimate for local control at 5 years was 77.2% (95% confidence interval [CI], 53.29%-89.91%). All marginal recurrences were successfully retreated whereas 6 of 15 patients with central recurrence developed subsequent re-recurrence following salvage EPBT. Median (range) visual acuity was 20/70 (20/20 to counting fingers at 1 foot) at time of recurrence and declined to counting fingers (20/25 to hand motion) at the most recent follow-up examination. Kaplan-Meier estimate for absence of metastatic disease at 5 years was 78.5% (95% CI, 54.77%-90.70%). CONCLUSIONS: Repeat I-125 EPBT offers a viable alternative to enucleation in patients with local recurrence of PUM, yielding high rates of local control with predictable decline in visual acuity.


Subject(s)
Brachytherapy/methods , Melanoma/radiotherapy , Uveal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Incidence , Iodine Radioisotopes/therapeutic use , Kaplan-Meier Estimate , Male , Melanoma/diagnosis , Melanoma/mortality , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Retrospective Studies , Sclera , Survival Rate/trends , Tennessee/epidemiology , Time Factors , Treatment Outcome , Uvea/diagnostic imaging , Uveal Neoplasms/diagnosis , Uveal Neoplasms/mortality , Visual Acuity
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