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Allen S Ho,
Gabriel J Tsao,
Frank W Chen,
Tianjie Shen,
Michael J Kaplan,
A Dimitrios Colevas,
Nancy J Fischbein,
Andrew Quon,
Quynh-Thu Le,
Harlan A Pinto,
Willard E Fee,
John B Sunwoo,
Davud Sirjani, Wendy Hara,
Mike Yao
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ABSTRACT: BACKGROUND: In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months. METHODS: A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans. RESULTS: PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive. CONCLUSIONS: HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation. Cancer 2012. © 2012 American Cancer Society.
Cancer 12/2012; · 4.77 Impact Factor
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ABSTRACT: OBJECTIVES:: To report outcomes, failure patterns, and toxicity after stereotactic radiosurgery (SRS) for recurrent head and neck cutaneous squamous cell carcinoma with gross perineural invasion (GPNI). METHODS:: Ten patients who received SRS as part of retreatment for recurrent head and neck cutaneous squamous cell carcinoma with GPNI were included. All patients exhibited clinical and radiologic evidence of GPNI before SRS. Previous treatments included surgery alone in 3 patients and surgery with adjuvant external beam radiotherapy (EBRT) in 7 patients. Retreatment included SRS alone in 2 and EBRT boosted with SRS in 8 patients. Magnetic resonance images were obtained every 3 to 6 months after SRS to track failure patterns. RESULTS:: At a median 22-month follow-up, the 2-year progression-free and overall survival rates were 20% and 50%, respectively. Seven patients exhibited local failures, all of which occurred outside both SRS and EBRT fields. Five local failures occurred in previously clinically uninvolved cranial nerves (CNs). CN disease spreads through 3 distinct patterns: among different branches of CN V; between CNs V and VII; and between V1 and CNs III, IV, and/or VI. Five patients experienced side effects potentially attributable to radiation. CONCLUSIONS:: Although there is excellent in-field control with this approach, the rate of out-of-field failures remains unacceptably high. We found that the majority of failures occurred in previously clinically uninvolved CNs often just outside treatment fields. Novel treatment strategies targeting this mode of perineural spread are needed.
American journal of clinical oncology 04/2012; · 2.21 Impact Factor
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Jose G Bazan, Wendy Hara,
Annie Hsu,
Pamela A Kunz,
James Ford,
George A Fisher,
Mark L Welton,
Andrew Shelton,
Daniel S Kapp,
Albert C Koong,
Karyn A Goodman,
Daniel T Chang
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ABSTRACT: The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).
Forty-six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty-five patients received 5-fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow-up was 26 months (CRT) and 32 months (IMRT). T3-T4 stage (P = .18) and lymph node-positive disease (P = .6) were similar between groups.
The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3-year overall survival (OS), locoregional control (LRC), and progression-free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC.
The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal.
Cancer 02/2011; 117(15):3342-51. · 4.77 Impact Factor
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Christopher H Chapman,
John Shen,
Edith J Filion,
Phuoc T Tran, Wendy Hara,
Alfredo Asuncion,
Daniel Marko,
Heather Wakelee,
Gerald J Berry,
Kevin W Dimmick,
Billy W Loo,
Jon Green
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2009; 4(12):1587-9. · 4.55 Impact Factor
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ABSTRACT: Nasopharyngeal carcinoma (NPC) has a bimodal age distribution. In contrast to the adult variant, little is known about the juvenile form. This study examined the treatment results between adult (aNPC) and juvenile NPC (jNPC) patients for future treatment considerations in jNPC.
The jNPC population included 53 patients treated at two institutions between 1972 and 2004. The aNPC population included 84 patients treated at one institution. The patients had received a median dose of 66 Gy of external beam radiotherapy and 72% underwent chemotherapy. The mean follow-up for surviving patients was 12.6 years for jNPC and 6.6 years for aNPC.
The jNPC patients presented with more advance stages than did the aNPC patients (92% vs. 67% Stage III-IV, p = .006). However, jNPC patients had significantly better overall survival (OS) than did aNPC patients. The 5-year OS rate was 71% for jNPC and 58% for aNPC (p = .03). The jNPC group also demonstrated a trend for greater relapse-free survival than the aNPC group (5-year relapse-free survival rate, 69% vs. 49%; p = .056). The pattern of failure analysis revealed that the jNPC patients had greater locoregional control and freedom from metastasis but the differences were not statistically significant. Univariate analysis for OS revealed that age group, nodal classification, and chemotherapy use were significant prognostic factors. Age group remained significant for OS on multivariate analysis, after adjusting for N classification and treatment.
Despite more advance stage at presentation, jNPC patients had better survival than did aNPC patients. Future treatment strategies should take into consideration the long-term complications in these young patients.
International journal of radiation oncology, biology, physics 04/2009; 75(4):1064-70. · 4.59 Impact Factor
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ABSTRACT: To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.
We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.
The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).
CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.
Neurosurgery 03/2009; 64(2 Suppl):A26-32. · 2.79 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.
METHODS: We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.
RESULTS: The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).
CONCLUSION: CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.
Neurosurgery 01/2009; 64(2):A26-A32. · 2.79 Impact Factor
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ABSTRACT: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).
Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.
At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.
Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.
International Journal of Radiation OncologyBiologyPhysics 07/2008; 71(2):393-400. · 4.11 Impact Factor
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ABSTRACT: To analyze the outcomes of and identify prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for locally advanced and recurrent soft-tissue sarcoma in adults from a single institution.
We retrospectively reviewed 50 consecutive patients treated with IORT to 62 sites of disease. Primary sites included retroperitoneum-pelvis (78%), extremity (8%), and other (14%). Seventy percent of patients had recurrent disease failing prior surgery (70%) and/or radiation (32%). Mean disease-free interval (DFI) before IORT was 1.9 years (range, 2 weeks-5.4 years). The IORT was delivered with orthovoltage X-rays using individually sized beveled cone applicators. Clinical characteristics were as follows: mean tumor size, 10 cm (range, 1-25 cm); high-grade histologic subtype (72%); and mean dose, 1,159 cGy (range, 600-1,600 cGy). Postoperative radiation or chemotherapy was administered to 37% of IORT Sites and 32% of patients, respectively. Outcomes measured were infield control (IFC), locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Mean and median follow-up of alive patients were 59 and 35 months, respectively.
Kaplan-Meier 5-year IFC, LRC, DMFS, and DSS probabilities for the entire group were 55%, 26%, 51%, and 25%, respectively. Prognostic factors found to be significant (p < 0.05) on multivariate analysis were prior DFI and tumor size for LRC, extremity location and leiomyosarcoma histologic subtype for DMFS, and prior DFI for DSS. Our cohort had five Grade 3/4 complications associated with treatment or a 5-year Kaplan-Meier Grade 3/4 complication-free survival rate of 85%.
IORT after tumor reductive surgery is well tolerated and seems to confer IFC in carefully selected patients.
International journal of radiation oncology, biology, physics 04/2008; 72(4):1146-53. · 4.59 Impact Factor
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ABSTRACT: Defined by its high level of accuracy and rapid radiation dose fall-off, radiosurgery has emerged as an effective radiation technique over the past few decades. Although it was once limited to conditions of the brain, head and neck regions, technological advances in computing and imaging have allowed the application of radiosurgery to conditions throughout the entire body. Using advanced imaging and robotics, the CyberKnife (Accuray, Inc., Sunnyvale, CA, USA) is one of few systems capable of delivering radiosurgery with exquisite accuracy to tumors, cancers and other conditions throughout the body. This review focuses on the development, technology, clinical efficacy and future directions of the CyberKnife.
Expert Review of Anti-infective Therapy 12/2007; 7(11):1507-15. · 2.65 Impact Factor
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Percy Lee,
Dilani K Weerasuriya,
Philip W Lavori,
Andrew Quon, Wendy Hara,
Peter G Maxim,
Quynh-Thu Le,
Heather A Wakelee,
Jessica S Donington,
Edward E Graves,
Billy W Loo
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ABSTRACT: In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging.
We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV).
The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant (p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS.
In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively.
International Journal of Radiation OncologyBiologyPhysics 11/2007; 69(2):328-33. · 4.11 Impact Factor
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ABSTRACT: To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution.
We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications.
The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p <or= 0.05) were the disease-free interval for LRC, tumor size for DMFS, and cervical primary, previous surgery, and locoregional relapse for DSS. Our cohort had 10 Grade 3-4 complications associated with treatment (surgery and IORT) and a Kaplan-Meier 5-year Grade 3-4 complication-free survival rate of 72%.
Survival for pelvic recurrence of gynecologic cancer is poor (range, 0-25%). IORT after surgery seems to confer long-term local control in carefully selected patients.
International Journal of Radiation OncologyBiologyPhysics 10/2007; 69(2):504-11. · 4.11 Impact Factor
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ABSTRACT: To study the impact on nodal coverage and dose to fixed organs at risk when using daily fiducial localization of the prostate to deliver intensity-modulated radiotherapy (IMRT).
Five patients with prostate cancer in whom prostate and pelvic nodes were irradiated with IMRT were studied. Dose was prescribed such that 95% of the prostate planning target volume (PTV) and 90% of the nodal PTV were covered. Random and systematic prostate displacements in the anterior-posterior, superior-inferior, and left-right directions were simulated to shift the original isocenter of the IMRT plan. The composite dose during the course of treatment was calculated.
Compared with a static setup, simulating random shifts reduced dose by less than 1.5% for nodal hotspot (i.e., dose to 1 cm(3)), by less than 1% for the 90% nodal PTV coverage, and by less than 0.5% for the nodal mean dose. Bowel and femoral head hotspots were reduced by less than 1.5% and 2%, respectively. A 10-mm systematic offset reduced nodal coverage by up to 10%.
The use of prostate fiducials for daily localization during IMRT treatment results in negligible changes in dose coverage of pelvic nodes or normal tissue sparing in the absence of a significant systematic offset. This offers a simple and practical solution to the problem of image-guided radiotherapy for prostate cancer when including pelvic nodes.
International Journal of Radiation OncologyBiologyPhysics 08/2007; 68(3):898-902. · 4.11 Impact Factor