Dwight E. Heron

Conventional 3D conformal versus intensity-modulated radiotherapy for the adjuvant treatment of gynecologic malignancies: a comparative dosimetric study of dose–volume histograms☆

OBJECTIVE The goals of this study were to evaluate the feasibility of pelvic intensity-modulated radiotherapy (IMRT) in the adjuvant treatment of gynecologic malignancies and to compare the dose-volume histograms (DVHs) and determine the potential impact on acute and long-term toxicity based on the dose to target and nontarget tissues for both planning techniques. METHODS Ten consecutive patients referred for adjuvant radiotherapy for gynecologic malignancies at the University of Pittsburgh School of Medicine and Magee-Womens Hospital were selected for CT-based treatment planning using the ADAC 3D version 4.2g and the NOMOS Corvus IMRT version 4.0. Normal tissues and critical structures were contoured on axial CT slices by both systems in conjunction with a gynecologic radiologist. These regions included internal, external, and common iliac nodal groups, rectum, upper 4 cm of vagina, bladder, and small bowel. Conventional treatment planning included 3D four-field box using 18-MV photons designed to treat a volume from the L(5)/S(1) border superiorly to the bottom of the ischial tuberosity on the AP/PA field and shaped blocks on the lateral fields to minimize the dose to the rectum and small bowel. A seven-field technique using 6-MV photons was used for IMRT. Restraints on small bowel for IMRT were set at 23.0 Gy +/- 5% and 35.0 Gy+/- 5% for the rectum and 37.5 Gy +/- 5% for the bladder while simultaneously delivering full dose (45.0 Gy) to the intrapelvic nodal groups in 1.8-Gy daily fractions. The dose-volume histograms where then compared for both treatment delivery systems. RESULTS The volume of each organ of interest (small bowel, bladder, and rectum) receiving doses in excess of 30 Gy was compared in the 3D and IMRT treatment plans. The mean volume of small bowel receiving doses in excess of 30 Gy was reduced by 52% with IMRT compared with 3D. A similar advantage was noted for the rectum (66% reduction) and the bladder (36% reduction). The nodal regions at risk and the upper vagina all received the prescribed dose of 45.0 Gy. CONCLUSIONS Intensity-modulated radiotherapy appears to offer several advantages over conventional 3D radiotherapy (3D CRT) planning for adjuvant radiotherapy for gynecologic malignancies. These include a significant reduction in treatment volume for bladder, rectum, and small bowel. It is anticipated that this reduction in volume of normal tissue irradiated would translate into overall reduction in acute and potentially late treatment-related toxicity. Prospective trials are necessary to better evaluate the advantages in a larger group of patients.

Stereotactic Body Radiotherapy for Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of a Phase I Dose-Escalation Trial

PURPOSE To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [(18)F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT). RESULTS No Grade 3/4 or dose-limiting toxicities occurred. Four patients had Grade 1/2 acute toxicities. Four objective responses were observed, for a response rate of 17% (95% confidence interval 2%-33%). The maximum duration of response was 4 months. Twelve patients had stable disease. Median time to disease progression was 4 months, and median overall survival was 6 months. Self-reported quality of life was not significantly affected by treatment. Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes. CONCLUSION Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies.

Induction Docetaxel, Cisplatin, and Cetuximab Followed by Concurrent Radiotherapy, Cisplatin, and Cetuximab and Maintenance Cetuximab in Patients With Locally Advanced Head and Neck Cancer

PURPOSE We incorporated cetuximab, a chimeric monoclonal antibody against the epidermal growth factor receptor (EGFR), into the induction therapy and subsequent chemoradiotherapy of head and neck cancer (HNC). PATIENTS AND METHODS Patients with locally advanced HNC, including squamous and undifferentiated histologies, were treated with docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and cetuximab 250 mg/m2 days 1, 8, and 15 (after an initial loading dose of 400 mg/m2), termed TPE, repeated every 21 days for three cycles, followed by radiotherapy with concurrent cisplatin 30 mg/m2 and cetuximab weekly (XPE), and maintenance cetuximab for 6 months. Quality of life (QOL) was assessed using Functional Assessment of Cancer Therapy-Head and Neck. In situ hybridization (ISH) for human papillomavirus (HPV), immunohistochemistry for p16, and fluorescence ISH for EGFR gene copy number were performed on tissue microarrays. RESULTS Of 39 enrolled patients, 36 had stage IV disease and 23 an oropharyngeal primary. Acute toxicities during TPE included neutropenic fever (10%) and during XPE, grade 3 or 4 oral mucositis (54%) and hypomagnesemia (39%). With a median follow-up of 36 months, 3-year progression-free survival and overall survival were 70% and 74%, respectively. Eight patients progressed in locoregional sites, three in distant, and one in both. HPV positivity was not associated with treatment efficacy. No progression-free patient remained G-tube dependent. The H&N subscale QOL scores showed a significant decrement at 3 months after XPE, which normalized at 1 year. CONCLUSION This cetuximab-containing regimen resulted in excellent long-term survival and safety, and warrants further evaluation in both HPV-positive and -negative HNC.

Deferring Planned Neck Dissection Following Chemoradiation for Stage IV Head and Neck Cancer: The Utility of PET-CT†

Objective: To determine whether combined positron emission tomography and computed tomography (PET‐CT) may be of value in deferring planned neck dissections for patients with advanced head and neck squamous cell carcinoma (HNSCC).

Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas.

Objectives: The aim of the study was to assess the feasibility and safety of stereotactic body radiotherapy (SBRT) in patients with advanced pancreatic adenocarcinoma. Methods: We reviewed outcomes of 71 patients treated with SBRT for pancreatic cancer between July 2004 and January 2009. Forty patients (56%) had locally unresectable disease, 11 patients (16%) had local recurrence following surgical resection, 8 patients (11%) had metastatic disease, and 12 patients (17%) received adjuvant SBRT for positive margins. The median dose was 24 Gy (18–25 Gy), given in a single-fraction SBRT (n = 67) or fractionated SBRT (n = 4). Kaplan-Meyer survival analyses were used to estimate freedom from local progression (FFLP) and overall survival (OS) rates. Results: The median follow-up among surviving patients was 12.7 months (4–26 months). The median tumor volume was 17 mL (5.1–249 mL). The overall FFLP rates at 6 months/1 year were 71.7%/48.5%, respectively. Among those with macroscopic disease, FFLP was achieved in 77.3% of patients with tumor size <15 mL (n = 22), and 59.5% for ≥15 mL (n = 37) (P = 0.02). FFLP was achieved in 73% following 24 to 25 Gy, and 45% with 18 to 22 Gy (P = 0.004). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%, respectively. Grade 1–2 acute and late GI toxicity were seen in 39.5% of patients. Three patients experienced acute grade 3 toxicities. Conclusions: SBRT is feasible, with minimal grade ≥3 toxicity. The overall FFLP rate for all patients was 64.8%, comparable to rates with external beam radiotherapy. This shorter treatment course can be delivered without delay in adjuvant systemic therapy.

Frameless stereotactic radiosurgery for recurrent head and neck carcinoma.

The aim of this study was to assess the feasibility and toxicity of stereotactic radiosurgery (CK-SRS) using the CyberKnife® Frameless Radiosurgery System (Accuray Inc., Sunnyvale, CA) in the management of recurrent squamous cell carcinoma of the head and neck region (SCCHN). Between November 2001 and February 2004, 22 patients with recurrent, previously irradiated SCCHN were treated with CK-SRS. The following endpoints were assessed post-CK-SRS: local control (LC), cause-specific survival (CSS), overall survival (OS), symptom relief, and acute and late toxicity. Kaplan-Meier survival analyses were used to estimate the LC, CSS, and OS rates. Clinical symptoms were graded as “improved,” “stable,” or “progressed” after CK-SRS. Acute and late toxicity were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) scale, version 2.0. Seventeen patients were followed until their death. The median follow-up in the remaining five patients was 19 months (range 11–40 months). The median survival time for the entire cohort was 12 months from the time of CK-SRS. The 2-year LC, CSS, and OS rates were 26%, 26%, and 22%, respectively. After CK-SRS, symptoms were improved or stable in all but one patient who reported increasing pain. The treatment was well tolerated, with one case each of Grade 2 and 3 mucositis. There were no acute Grade 4 or 5 CTC toxicities. There were no late toxicities in this cohort. Frameless stereotactic radiosurgery for recurrent SCCHN is feasible and safe in the setting of high doses of prior irradiation. The majority of patients experienced palliation of disease without excess toxicity.

Concurrent cetuximab with stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: a single institution matched case-control study.

Purpose:Locally recurrent head and neck squamous cell carcinoma can be treated with curative intent by surgical salvage or reirradiation with or without chemotherapy. We have previously demonstrated the feasibility and safety of stereotactic body reirradiation at our institution; however, efficacy has been unsatisfactory. Based on the successful combination of cetuximab with radiotherapy in locally-advanced squamous cell carcinoma of the head and neck, we compared stereotactic body radiotherapy alone with combination therapy, using concomitant cetuximab with stereotactic body radiotherapy, to enhance clinical efficacy while minimizing toxicity. Methods:In a retrospective-matched cohort study, we compared 2 groups of patients treated over a 6-year period with stereotactic body radiation therapy alone (n = 35) or with weekly cetuximab infusion during stereotactic body radiotherapy (n = 35), and evaluated clinical response, local control, overall survival, and toxicity. Cox proportional hazard models were used to assess independent prognostic factors. Results:The median follow-ups for patients alive at last contact were 21.3 months and 24.8 months for stereotactic body radiotherapy only (n = 13) and stereotactic body radiotherapy plus cetuximab (n = 22), respectively. Our results indicate that cetuximab conferred an overall survival advantage (24.5 vs. 14.8 months) when compared with the stereotactic body radiotherapy alone arm, without a significant increase in grade 3/4 toxicities. This survival advantage was also observed in the subgroup that had received cetuximab therapy during their prior therapeutic regimen. Conclusions:Our results suggest an overall survival benefit of concomitant cetuximab with stereotactic body radiotherapy in locally recurrent head and neck squamous cell carcinoma, and suggest a role in this setting. Concomitant cetuximab with stereotactic body radiotherapy is a reasonable approach for unresectable recurrent squamous cell carcinoma of the head and neck, and should be tested in prospective randomized trials to validate its clinical efficacy.

Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning.

PURPOSE The aim of this study was to assess the outcomes of patients treated with stereotactic body radiation therapy (SBRT) in patients with primary, recurrent, or metastatic lung lesions, with a focus on positron emission tomography (PET)/computed tomography (CT)-based management. PATIENTS AND METHODS Fifty-one patients with primary stage I non-small-cell lung cancer (NSCLC; n = 26), recurrent lung cancer after definitive treatment (n = 12), or solitary lung metastases (n = 13) were treated with SBRT between 2005 and 2007. Patients were treated with the CyberKnife Robotic Radiosurgery System with Synchrony respiratory tracking. A dose of 60 Gy was delivered in 3 fractions. All patients had CT or PET/CT performed at approximately 3-month intervals after treatment. RESULTS The median follow-up was 12 months. Local control at median follow-up was 85% in patients with stage I NSCLC, 92% in patients with recurrent lung cancer, and 62% in the patients with solitary lung metastasis. Analysis of the 28 patients with pre- and post-treatment PET/CT scans demonstrated that those with stable disease (n = 4) had a mean standardized uptake value (SUV) decrease of 28%, partial responders (n = 11) had a decrease of 48%, and patients with a complete response (n = 11) had a decrease of 94%. Patients with progressive disease (n = 2) had an SUV decrease of only 0.4%. Only 2 patients (7%) who had reduced fluorodeoxyglucose avidity later progressed locally. No correlations were found between pretreatment SUV and tumor response, disease progression, or survival. Overall 1-year survival rates were 81%, 67%, and 85% among the patients with primary NSCLC, recurrent lung cancer, and solitary lung metastases, respectively. CONCLUSION Stereotactic body radiation therapy with CyberKnife is an effective treatment for patients with medically inoperable recurrent or metastatic lung cancer. Positron emission tomography/CT is valuable in staging, planning, and evaluating treatment response and might predict long-term outcome.

Efficacy and cost-effectiveness analysis of external beam and stereotactic body radiation therapy in the treatment of spine metastases: a matched-pair analysis

OBJECT The objective of this study was to compare the palliative efficacy and cost effectiveness of external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) as primary treatment for bone metastatic disease of the spinal column. METHODS Forty-four patients were matched based on age, primary tumor site, year of treatment, and location of metastasis. Outcomes of interest were pain relief, cost-effectiveness, toxicities, and need for further intervention. Pain relief was rated as excellent, good, fair, or poor, using a radiosurgical pain scale to combine visual analog scale and verbal descriptor ordinal scale scores. Medicare fee schedules were used to compute the charges for both the technical and professional components of care. Patients in the EBRT group were treated using a linear accelerator while patients in the SBRT group were treated with the CyberKnife robotic radiosurgery system. Patients received regular follow-up evaluations by a radiation oncologist and neurosurgeon. RESULTS Forty-four patients (22 pairs) were analyzed. At a follow-up of 1 month, there was no statistically significant difference in pain between the 2 groups (p = 0.11). Patients who underwent SBRT had the highest total gross charge; depending on technique, EBRT treatments ranged from 29% to 71% of the SBRT charge. Patients treated using EBRT had more acute toxicities, and more of these patients underwent further intervention at the treated spinal level. There were no late complications attributed to either treatment modality. CONCLUSIONS External beam radiation therapy remains an efficacious and cost-effective method of palliation of spine metastases. In this study, patients treated with EBRT had more acute toxicities and were more likely to require additional interventions at the treated sites. Stereotactic body radiation therapy, although more costly, resulted in comparable rates of pain relief and late treatment-related toxicity, and continues to show promise as an emerging modality for selected patients with spine metastases.

PET-CT in radiation oncology: the impact on diagnosis, treatment planning, and assessment of treatment response.

Objective:To review the role of hybrid positron emission tomography (PET)-computed tomography (CT) systems in the design and management of cancer patients in the modern radiation oncology practice. PET is co-registered with CT and incorporated into a systematic approach to the staging, management, and assessment of response and surveillance of a variety of oncologic diagnoses. Methods:A review of the literature of functional imaging such as PET-CT in staging, treatment plan design, assessment of response and detection of recurrence for tumors involving the head and neck, lung, esophagus, rectum amongst others. Results:PET and PET-CT offer significant advantages which include more accurate staging which often results in management changes in roughly one-third of patients across a number of disease site. More accurate target definition may augment highly conformal radiation treatment plans using intensity-modulated radiation therapy and stereotactic radiosurgery and radiotherapy. Conclusion:The emerging data appears to suggest the functional imaging may be a more useful tool to evaluate the therapeutic effect of treatment, detect early failures and prognosticate long-term outcome.