ABSTRACT
PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.
Subject(s)
Chemoradiotherapy , Cisplatin , Endometrial Neoplasms , Neoplasm Recurrence, Local , Humans , Female , Endometrial Neoplasms/radiotherapy , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/therapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Aged , Prospective Studies , Chemoradiotherapy/methods , Progression-Free Survival , Adult , Brachytherapy/methods , Brachytherapy/adverse effects , Antineoplastic Agents/therapeutic useABSTRACT
Hepatocellular carcinoma is the fourth leading cause of cancer-related death worldwide. Depending on the extent of disease and competing comorbidities for mortality, multiple liver-directed therapy options exist for the treatment of hepatocellular carcinoma. Advancements in radiation oncology have led to the emergence of stereotactic body radiation therapy as a promising liver-directed therapy, which delivers high doses of radiation with a steep dose gradient to maximize local tumor control and minimize radiation-induced treatment toxicity. In this study, we review the current clinical data as well as the unresolved issues and controversies regarding stereotactic body radiation therapy for hepatocellular carcinoma: (1) Is there a radiation dose-response relationship with hepatocellular carcinoma? (2) What are the optimal dosimetric predictors of radiation-induced liver disease, and do they differ for patients with varying liver function? (3) How do we assess treatment response on imaging? (4) How does stereotactic body radiation therapy compare to other liver-directed therapy modalities, including proton beam therapy? Based on the current literature discussed, this review highlights future possible research and clinical directions.
Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Dose-Response Relationship, Radiation , Humans , Liver/radiation effects , Radiosurgery/methods , Treatment OutcomeABSTRACT
OBJECTIVE: Dosimetric evaluation of air column in gastrointestinal (GI) structures in intensity modulated radiation therapy (IMRT) of pancreatic cancer. METHODS: Nine sequential patients were retrospectively chosen for dosimetric analysis of air column in the GI apparatus in pancreatic cancer using cone beam CT (CBCT). The four-dimensional CT (4DCT) was used for target and organs at risk (OARs) and non-coplanar IMRT was used for treatment. Once a week, these patients underwent CBCT for air filling, isocentre verification and dose calculations retrospectively. RESULTS: Abdominal air column variation was as great as ±80% between weekly CBCT and 4DCT. Even with such a large air column in the treatment path for pancreatic cancer, changes in anteroposterior dimension were minimal (2.8%). Using IMRT, variations in air column did not correlate dosimetrically with large changes in target volume. An average dosimetric deviation of mere -3.3% and a maximum of -5.5% was observed. CONCLUSION: CBCT revealed large air column in GI structures; however, its impact is minimal for target coverage. Because of the inherent advantage of segmentation in IMRT, where only a small fraction of a given beam passes through the air column, this technique might have an advantage over 3DCRT in treating upper GI malignancies where the daily air column can have significant impact. Advances in knowledge: Radiation treatment of pancreatic cancer has significant challenges due to positioning, imaging of soft tissues and variability of air column in bowels. The dosimetric impact of variable air column is retrospectively studied using CBCT. Even though, the volume of air column changes by ± 80%, its dosimetric impact in IMRT is minimum.
Subject(s)
Cone-Beam Computed Tomography , Gastrointestinal Tract/diagnostic imaging , Pancreatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Female , Four-Dimensional Computed Tomography , Humans , Male , Organs at Risk , Patient Positioning , Radiotherapy Dosage , Retrospective StudiesABSTRACT
OBJECTIVES: Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. METHODS: Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. RESULTS: The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. CONCLUSION: Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.
Subject(s)
Adenocarcinoma/therapy , Antimetabolites, Antineoplastic/therapeutic use , Chemoradiotherapy , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/therapy , Pancreaticoduodenectomy , Aged , Chemotherapy, Adjuvant , Combined Modality Therapy , Deoxycytidine/therapeutic use , Female , Humans , Indiana , Male , Middle Aged , Retrospective Studies , Universities , GemcitabineABSTRACT
Small bowel dose often represents a limiting factor for radiation treatment of pelvic malignancies. To reduce small bowel toxicity, a belly board device (BBD) with a prone position is often recommended. Intensity modulated radiotherapy (IMRT) could reduce dose to small bowel based on the desired dose-volume constraints. We investigated the efficacy of BBD in conjunction with IMRT. A total of 11 consecutive patients with the diagnosis of rectal cancer, who were candidates for definitive therapy, were selected. Patients were immobilized with BBD in prone position for simulation and treatment. Supine position computed tomography (CT) data were either acquired at the same time or during a diagnostic scan, and if existed was used. Target volumes (TV) as well as organs at risk (OAR) were delineated in both studies. Three-dimensional conformal treatment (3DCRT) and IMRT plans were made for both scans. Thus for each patient, 4 plans were generated. Statistical analysis was conducted for maximum, minimum, and mean dose to each structure. When comparing the normalized mean Gross TV dose for the different plans, there was no statistical difference found between the planning types. There was a significant difference in small bowel sparing when using prone position on BBD comparing 3DCRT and IMRT plans, favoring IMRT with a 29.6% reduction in dose (p = 0.007). There was also a statistically significant difference in small bowel sparing when comparing supine position IMRT to prone-BBD IMRT favoring prone-BBD IMRT with a reduction of 30.3% (p = 0.002). For rectal cancer when small bowel could be a limiting factor, prone position using BBD along with IMRT provides the best sparing. We conclude that whenever a dose escalation in rectal cancer is desired where small bowel could be limiting factor, IMRT in conjunction with BBD should be selected.
Subject(s)
Pelvis/radiation effects , Radiotherapy, Intensity-Modulated/instrumentation , Rectal Neoplasms/radiotherapy , Adult , Aged , Female , Humans , Male , Middle Aged , Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
PURPOSE: To evaluate long-term outcome and toxicity of stereotactic body radiation therapy (SBRT) for hepatic oligometastases from solid tumors. METHODS AND MATERIALS: Eligible patients had 1 to 3 liver metastases, maximum sum diameter 6 cm, without extrahepatic progression. We treated 106 lesions in 81 patients; 67% with colorectal primaries. Median dose was 5400 cGy in 3 to 5 fractions. RESULTS: At median follow-up of 33 months (2.5-70 months), overall local control was 94% (95% confidence interval, not estimable); Kaplan-Meier estimated 96% at 1 year and 91% at 2, 3, and 4 years. Partial/complete response was observed in 69% of lesions with less than 3% progressing. Median survival time was 33.6 months (95% confidence interval, 29.1-38.4); Kaplan-Meier survival estimates at 1, 2, 3, and 4 years were 89.9%, 68.6%, 44.0%, and 28.0%, respectively. Grade 3 or greater liver toxicity was 4.9%. CONCLUSION: SBRT is effective for selected patients with hepatic oligometastases with limited toxicities. A phase 3 trial comparing SBRT with "gold-standard" surgical resection is warranted.
Subject(s)
Liver Neoplasms/secondary , Liver Neoplasms/surgery , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Radiosurgery/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients received gemcitabine 1000 mg/m(2) intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m(2) intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). RESULTS: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K(trans) in responding patients. CONCLUSIONS: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.
Subject(s)
Adenocarcinoma/therapy , Antineoplastic Agents/adverse effects , Chemoradiotherapy/methods , Deoxycytidine/analogs & derivatives , Niacinamide/analogs & derivatives , Pancreatic Neoplasms/therapy , Phenylurea Compounds/adverse effects , Radiotherapy, Intensity-Modulated/methods , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/pharmacokinetics , Disease-Free Survival , Dose Fractionation, Radiation , Drug Administration Schedule , Female , Genotype , Humans , Induction Chemotherapy/methods , Magnetic Resonance Imaging/methods , Male , Maximum Tolerated Dose , Middle Aged , Niacinamide/administration & dosage , Niacinamide/adverse effects , Niacinamide/pharmacokinetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/pharmacokinetics , Polymorphism, Single Nucleotide/genetics , Prospective Studies , Sorafenib , Tumor Burden , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , GemcitabineABSTRACT
Recently, stereotactic body radiotherapy (SBRT) for lung cancer is conducted with heterogeneity-corrected treatment plans, as the correction greatly affects the dose delivery to the lung tumor. In this study, the correlation between the planning target volume (PTV) and the dose delivery is investigated by separation of the heterogeneity correction effects into photon attenuation and electron transport. Under Institutional Review Board exemption status, 74 patients with lung cancer who were treated with SBRT were retrospectively evaluated. All treatment plans were generated using an anisotropic analytical algorithm (AAA) of an Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system. Two additional plans were created using the same treatment parameters (monitor units, beam angles and energy): a plan with no heterogeneity correction (NC), and a plan calculated with a pencil beam convolution algorithm (PBC). Compared with NC, AAA and PBC isocenter doses were on average 13.4% and 21.8% higher, respectively. The differences in the isocenter dose and the dose coverage for 95% of the PTV (D95%) between PBC and AAA were correlated logarithmically (ρ = 0.78 and ρ = 0.46, respectively) with PTV. Although D95% calculated with AAA was in general 2.9% larger than that for NC, patients with a small PTV showed a negative ΔD95% for AAA due to the significant effect of electron transport. The PTV volume shows logarithmic correlation with the effects of the lateral electron transport. These findings indicate that the dosimetric metrics and prescription, especially in clinical trials, should be clearly evaluated in the context of target volume characteristics and with proper heterogeneity correction.
Subject(s)
Lung Neoplasms/surgery , Radiosurgery/statistics & numerical data , Algorithms , Electron Transport , Humans , Lung Neoplasms/pathology , Radiometry/statistics & numerical data , Retrospective StudiesABSTRACT
BACKGROUND: Epithelial growth factor receptor over-expression correlates with poor outcomes in cervical cancer. This study assessed the safety of chemoradiation with cetuximab in the treatment of women with newly diagnosed locally advanced cervical cancer. METHODS: Patients received weekly cisplatin 30 and 40 mg/m(2) [dose level (DL) 1 and 2] and cetuximab 400mg/m(2) loading dose and then 250 mg/m(2) for a total of six weeks with radiotherapy (RT). Patients with nodal metastases received extended field radiation therapy (EFRT). At the maximum tolerated dose, feasibility was evaluated in a 20 patient two-stage, sequential design. RESULTS: In patients receiving pelvic RT, seven were treated at DL 1 with one dose-limiting toxicity (DLT) (febrile neutropenia with grade 3 diarrhea) and three at DL 2 with two DLTs (grade 3 rash and delay in RT >8 weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there was one DLT (grade 4 CVA). Median RT duration was 50 days (range, 42-70). In patients receiving EFRT, nine were treated at DL 1 with 1 DLT (grade 3 mucositis) and 24 in the feasibility phase with eight DLTs [delay in RT >8 weeks due to toxicity (2) and one each with grade 3 or 4 small bowel obstruction, embolism, mucositis, mucositis with hypokalemia, pain with headache, and platelets with mucositis and headache]. Median EFRT duration was 56 days (range, 36-74). CONCLUSIONS: For patients receiving pelvic RT, cisplatin and cetuximab were feasible. For patients receiving EFRT, combination of cisplatin and cetuximab was not feasible.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Uterine Cervical Neoplasms/therapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Cetuximab , Cisplatin/administration & dosage , Cisplatin/adverse effects , Female , Humans , Lymphatic Metastasis , Middle AgedABSTRACT
OBJECTIVES: The definitive treatment of early-stage cervical cancer involves multidisciplinary decision making. This expert panel was convened to reach consensus on the selection of appropriate therapies based on patient and disease characteristics at presentation. METHODS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or the treatment. RESULTS: Three clinical variants were developed to represent common scenarios in the treatment of early-stage cervical cancer. Group members reached consensus on the appropriateness of therapeutic options. This process yielded numerical ratings and descriptive commentary. CONCLUSIONS: This manuscript represents the consensus opinion of an expert panel based on a survey of all available medical literature. This manuscript may be used to inform the clinical decision making of physicians involved in the treatment of early-stage cervical cancer.
Subject(s)
Diagnostic Imaging/standards , Practice Guidelines as Topic/standards , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/radiotherapy , Female , Humans , Neoplasm Staging , PrognosisABSTRACT
PURPOSE: To evaluate the dosimetric impact of rotational setup errors in stereotactic body radiotherapy (SBRT) treatment of liver tumors and to investigate whether translational shifts can compensate for rotation. METHODS AND MATERIALS: The positioning accuracy in 20 patients with liver malignancies treated with SBRT was reevaluated offline by matching the patients' cone-beam computed tomography (CT) scans (n=75) to the planning CT scans and adjusting the 3 rotational angles (pitch, roll, and yaw). Systematic and random setup errors were calculated. The dosimetric changes caused by rotational setup errors were quantified for both simulated and observed patient rotations. Dose distributions recalculated on the rotated CT scans were compared with the original planned doses. Translational corrections were simulated based on manual translational registration of the rotated images to the original CT scans. The correction efficacy was evaluated by comparing the recalculated plans with the original plans. RESULTS: The systematic rotational setup errors were -0.06° ± 0.68°, -0.29° ± 0.62°, and -0.24° ± 0.61°; the random setup errors were 0.80°, 1.05°, and 0.61° for pitch, roll, and yaw, respectively. Analysis of CBCT images showed that 56.0%, 14.7%, and 1.3% of treated fractions had rotational errors of >1°, >2°, and >3°, respectively, in any one of the rotational axes. Rotational simulations demonstrated that the reduction of gross tumor volume (GTV) coverage was <2% when rotation was <3°. Recalculated plans using actual patient roll motions showed similar reduction (<2%) in GTV coverage. Translational corrections improved the GTV coverage to within 3% of the original values. For organs at risk (OAR), the dosimetric impact varied case by case. CONCLUSION: Actual rotational setup errors in SBRT for liver tumors are relatively small in magnitude and are unlikely to affect GTV coverage significantly. Translational corrections can be optimized to compensate for rotational setup errors. However, caution regarding possible dose increases to OAR needs to be exercised.
Subject(s)
Cone-Beam Computed Tomography/methods , Liver Neoplasms/surgery , Organs at Risk/diagnostic imaging , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Setup Errors , Tumor Burden , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Organs at Risk/radiation effects , Radiotherapy Dosage , Radiotherapy Setup Errors/prevention & control , Retrospective Studies , Rotation , UncertaintyABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence due to hepatitis C. Stereotactic body radiotherapy (SBRT) is a noninvasive, effective therapy in the management of liver malignancies. The authors evaluated radiological response in 26 patients with HCC treated with SBRT at Indiana University. METHODS: Between March 2005 and June 2008, 26 patients with HCC who were not surgical candidates were enrolled in a phase 1 to 2 trial. Eligibility criteria included solitary tumors ≤ 6 cm or up to 3 lesions with sum diameters ≤ 6 cm, and well-compensated cirrhosis. All patients had imaging before, at 1 to 3 months, and every 3 to 6 months after SBRT. RESULTS: Patients received 3 to 5 fractions of SBRT. Median SBRT dose was 42 Gray (Gy) (range: 24-48 Gy). Median follow-up was 13 months. Per Response Evaluation Criteria in Solid Tumors (RECIST), 4 patients had a complete response (CR), 15 had a partial response (PR), and 7 achieved stable disease (SD) at 12 months. One patient with SD experienced progression marginal to the treated area. The overall best response rate (CR + PR) was 73%. In comparison, by European Association for the Study of the Liver (EASL) criteria, 18 of 26 patients had ≥ 50% nonenhancement at 12 months. Thirteen of 18 demonstrated 100% nonenhancement, being > 50% in 5 patients. Kaplan-Meier 1- and 2-year survival estimates were 77% and 60%, respectively. CONCLUSIONS: SBRT is effective therapy for patients with HCC with an overall best response rate (CR + PR) of 73%. Nonenhancement on imaging, a surrogate for ablation, may be a more useful indicator than size reduction in evaluating HCC response to SBRT in the first 6 to 12 months, supporting EASL criteria.
Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Radiosurgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
PURPOSE: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. RESULTS: The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no ≥Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. CONCLUSIONS: SBRT is a safe, effective, noninvasive option for patients with HCC ≤6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant.
Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Clinical Trials, Phase I as Topic , Disease-Free Survival , Dose Fractionation, Radiation , Female , Humans , Karnofsky Performance Status , Kidney/radiation effects , Liver Cirrhosis/pathology , Liver Cirrhosis/surgery , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation , Male , Middle Aged , Organs at Risk/radiation effects , Radiosurgery/adverse effects , Radiosurgery/mortality , Spinal Cord/radiation effects , Tumor Burden , Young AdultABSTRACT
Stereotactic body radiation therapy (SBRT) is gaining wide acceptance as a treatment modality for lung and liver tumors, and it is crucial to make an accurate evaluation of the local effects of ablative doses of radiation in terms of local tumor control and normal tissue reaction or damage. The very complex radiation dose distribution of SBRT, the use of a large number of non-opposing and noncoplanar beams, and the delivery of individual ablative doses of radiation may cause substantially different radiographic appearance on diagnostic imaging compared with conventional radiation therapy. Different patterns of radiographic changes have been observed in the lung and liver after SBRT. This article reviews the post-SBRT imaging changes in the lung and liver. Since computed tomography and PET are the most commonly used diagnostic imaging tools for monitoring lung tumor and computed tomography for liver tumors, this article will focus on the changes observed on those imaging modalities.
Subject(s)
Liver Neoplasms/surgery , Lung Neoplasms/surgery , Diagnostic Imaging/methods , Dose-Response Relationship, Radiation , Humans , Liver Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Radiosurgery/methodsABSTRACT
PURPOSE: To quantify the frequency of rib fracture and chest wall (CW) pain and identify the dose-volume parameters that predict CW toxicity after stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: The records of patients treated with SBRT between 2000 and 2008 were reviewed, and toxicity was scored according to Common Terminology Criteria for Adverse Events v3.0 for pain and rib fracture. Dosimetric data for CW and rib were analyzed and related to the frequency of toxicity. The risks of CW toxicity were then further characterized according to the median effective concentration (EC(50)) dose-response model. RESULTS: A total of 347 lesions were treated with a median follow-up of 19 months. Frequency of Grade I and higher CW pain and/or fracture for CW vs. non-CW lesions was 21% vs. 4%, respectively (p < 0.0001). A dose of 50 Gy was the cutoff for maximum dose (Dmax) to CW and rib above which there was a significant increase in the frequency of any grade pain and fracture (p = 0.03 and p = 0.025, respectively). Volume of CW receiving 15 Gy - 40 Gy was highly predictive of toxicity (R(2) > 0.9). According to the EC(50) model, 5 cc and 15 cc of CW receiving 40 Gy predict a 10% and 30% risk of CW toxicity, respectively. CONCLUSION: Adequate tumor coverage remains the primary objective when treating lung or liver lesions with SBRT. To minimize toxicity when treating lesions in close proximity to the CW, Dmax of the CW and/or ribs should remain <50 Gy, and <5 cc of CW should receive ≥ 40 Gy.
Subject(s)
Chest Pain/etiology , Liver Neoplasms/surgery , Lung Neoplasms/surgery , Radiosurgery/adverse effects , Rib Fractures/etiology , Thoracic Wall/radiation effects , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Radiation , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Radiation Injuries/etiology , Retrospective Studies , Young AdultABSTRACT
PURPOSE: Pigmented villonodular synovitis (PVNS) is an uncommon proliferative lesion of synovial tissue. In diffuse PVNS, recurrence rates are high after resection alone. Adjuvant external beam radiation therapy contributes to improved local control. Limited data exist for intra-articular radioisotope therapy after surgical resection. We report institutional experience with intra-articular chromic phosphate ((32)P). METHODS AND MATERIALS: Records were reviewed from the Department of Radiation Oncology at Indiana University. Nine cases of PVNS treated with (32)P were identified (mean age=40). Seven patients were treated at time of recurrence and 2 patients were treated prophylactically. Intra-articular injections were performed by accessing the joint space, aspirating joint fluid, reinjecting 1-2 mCi of (32)P, and barbitaging to ensure good distribution in the joint space. No external beam radiation therapy was delivered. One patient was lost to followup. Mean followup of remaining patients was 20 months (range, 2-48). RESULTS: Eleven injections were performed in 9 patients. Eight had PVNS in the knee(s) and 1 patient had involvement of the hip. Two patients were treated more than once, one for a recurrence in the same joint at 13 months and another for PVNS of a contralateral joint. Three clinical recurrences (2, 13, and 28 months) were noted. Two of three recurrences were in patients who had bulky diffuse PVNS at the time of injection. Overall local control was 70%. In patients without bulky diffuse PVNS at the time of injection, local control was 88%. CONCLUSION: We report success using intra-articular injections of (32)P after synovectomy in patients with PVNS.
Subject(s)
Brachytherapy/methods , Chromium Compounds/administration & dosage , Phosphates/administration & dosage , Synovitis/diagnosis , Synovitis/radiotherapy , Adult , Female , Humans , Injections, Intra-Articular , Knee Joint/radiation effects , Male , Middle Aged , Radiopharmaceuticals/administration & dosage , Treatment OutcomeABSTRACT
OBJECTIVE: A Phase II study was conducted at Indiana University to evaluate the safety and efficacy of combined weekly Gemcitabine (GEM) with external beam radiotherapy (RT) in unresectable, locally advanced pancreatic cancer (LAPC). METHODS: Eligible patients had biopsy-proven LAPC without evidence of metastatic disease. In part A of the treatment plan, patients received GEM 600 mg/m(2) IV weekly, with concurrent RT (50.4 Gy in 28 fractions, 1.8 Gy/d, 5 days per week). Part B of the treatment plan began approximately 4 weeks after completing part A: patients without disease progression received weekly GEM 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle for 6 cycles or until disease progression. RESULTS: From April 2001 to June 2003, of 28 patients evaluated, 24 (86%) completed part A. About 22 patients had grade 3 toxicities, primarily hematologic (43%) and gastrointestinal (36%). Three patients (11%) had grade 4 toxicities (one each for hyperbilirubinemia, infection, and dyspnea). The median follow-up was 10 months (1-63 months) for all enrolled patients. Six patients (21%) had a radiologic partial response, 16 (57%) had stable disease, 5 (18%) had progressive disease, and 1 patient (4%) had an unevaluable response at last follow-up. Four patients (14%) underwent surgical resection (2 with R0 resection). Median time to progression was 6 months (0-36 months). Median survival time was 10.3 months (95% confidence interval, 7.9-14.6 months). The 1- and 2-year actuarial survival rates were 30% and 11%. At last analysis, all but 2 patients died. CONCLUSION: The activity and toxicity profile of combination GEM and RT indicates that this can be safely administered for patients with LAPC.
Subject(s)
Adenocarcinoma/therapy , Antimetabolites, Antineoplastic/therapeutic use , Brachytherapy , Carcinoma, Adenosquamous/therapy , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/therapy , Adenocarcinoma/secondary , Adult , Aged , Carcinoma, Adenosquamous/secondary , Combined Modality Therapy , Deoxycytidine/therapeutic use , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Survival Rate , Treatment Outcome , GemcitabineABSTRACT
Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adults and it is frequently associated with cirrhosis. Surgical resection or orthotopic liver transplantation can be curative but only 30-40% of patients may benefit from curative radical treatment. Stereotactic body radiation therapy (SBRT) has emerged as a promising non-invasive therapy for patients with unresectable HCC and it may potentially serve as a bridging therapy for patients awaiting transplantation. There are a limited number of clinical trials examining the use of SBRT in patients with HCC and very good local tumor control and acceptable toxicities have been reported. This article provides an overview on the use of SBRT in the management of HCC.
Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Radiosurgery/methods , Clinical Trials as Topic , Humans , Patient Selection , Radiation Injuries/etiology , Radiosurgery/adverse effectsABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing. METHODS: A Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh's Class (CTP) A or B, were not candidates for resection, had 1-3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/ fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity. RESULTS: Seventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10-42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively. CONCLUSIONS: SBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual.
Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Radiosurgery/adverse effects , Radiosurgery/methods , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Male , Maximum Tolerated Dose , Middle AgedABSTRACT
PURPOSE: To evaluate the outcomes of surgically staged patients with Stage I-IIIA uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) of the uterus treated at Indiana University with intraperitoneal (32)P and vaginal brachytherapy. METHODS: Between 1997 and 2004, a total of 28 patients with Stage I-IIIA UPSC and CCC were treated with a standardized adjuvant therapy. All patients underwent comprehensive surgical staging with negative pelvic and para-aortic lymph nodes and no gross residual disease. After a Technetium-99m distribution study, (32)P was administered intraperitoneally. Subsequently, high dose rate (HDR) vaginal cuff brachytherapy was delivered to a total dose of 2100 cGy in three fractions prescribed to 0.5 cm depth. The records of these 28 patients were reviewed, including 18 patients who were treated on Hoosier Oncology Group 97-01 (Phase II trial), and whose followup was updated. RESULTS: Intraperitoneal (32)P was administered at a median of 4 weeks from surgery, followed by vaginal brachytherapy. One patient had no available followup information and is not included in the analysis. The median followup for the 27 evaluable patients was 40.9 months. No patients had Grade 2, 3, or 4 complications related to their adjuvant treatment. There were 4 patients with recurrent disease: 2 initially relapsed intraperitoneally, 1 in the distal vagina, and 1 had a scar recurrence. Three patients have died of the disease. For all 27 patients, the 3-year overall survival, cause-specific survival, and disease-free survival were 84.2%, 90.7%, and 74.4%, respectively. CONCLUSIONS: Adjuvant therapy for UPSC and CCC with intraperitoneal (32)P and vaginal brachytherapy after adequate surgical staging and maximal cytoreduction is well tolerated and appears to be effective. Further study is warranted.