Treatment outcomes for patients with chloroma receiving radiation therapy.

INTRODUCTION: This study aims to analyse treatment outcomes, disease control and toxicity in patients with chloromas referred for radiation therapy (RT). METHODS: Medical records were retrospectively reviewed for 41 patients with chloromas treated with RT at our institution. RESULTS: Twenty-five patients were treated with palliative intent, whereas sixteen received RT as a component of curative intent therapy in addition to systemic chemotherapy with or without haematopoietic stem cell transplant (HSCT). All patients received RT for chloroma (median dose 24 Gy). Median survival was 5.4 months after RT (95% confidence interval (CI) 3.5-12.6 months), and no significant difference in overall survival was identified based on prior treatment with systemic chemotherapy alone or HSCT. Patients treated with curative intent had a median survival of 26.2 months (95% CI 6.1-48.9 months) and a Kaplan-Meier estimate of 15% overall survival at 5 years. At the end of the study follow-up period, 38 patients were dead and three patients treated with curative intent remained alive. After palliative RT, 44% of patients experienced partial relief and 48% experienced complete symptomatic improvement without significant acute toxicities. CONCLUSIONS: RT provides timely symptom palliation for patients with chloromas with minimal morbidity, but the prognosis remains poor. Long-term remission can be achieved in selected patients with salvage chemotherapy and HSCT.

Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery.

Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.

Radiation therapy for breast cancer patients who undergo oncoplastic surgery: localization of the tumor bed for the local boost.

INTRODUCTION: Oncoplastic reconstructive surgery is performed in select patients with breast cancer to allow conservation treatment when the lumpectomy would be expected to have a poor cosmetic outcome. These techniques not only rearrange the breast tissue but may also shift the position of the tumor bed. The oncoplastic incision may have no relationship to the tumor bed. Although use of whole-breast radiation therapy (RT) is straightforward, difficulties in localization of the tumor bed for the local RT boost have not been investigated. MATERIALS AND METHODS: A retrospective review was performed of 25 patients with 26 cancers who received RT after breast conservation surgery with oncoplastic reconstruction. RESULTS: Among 11 patients with a minimum of 4 surgical clips placed at tumor resection, 8 (73%) had the final tumor bed extend beyond the original breast quadrant or be completely relocated into a different region. In 3 (27%) cases, the clinical treatment volume was 2 to 3 separated regions within the breast. DISCUSSION: For breast cancer patients who have had oncoplastic surgery, the tumor bed is frequently more extensive and possibly relocated compared with original presentation. Placement of surgical clips after tumor resection and before oncoplastic reconstruction may be the most accurate method to localize the RT local boost field.

Setup variations in radiotherapy of anal cancer: advantages of target volume reduction using image-guided radiation treatment.

PURPOSE: To define setup variations in the radiation treatment (RT) of anal cancer and to report the advantages of image-guided RT (IGRT) in terms of reduction of target volume and treatment-related side effects. METHODS AND MATERIALS: Twelve consecutive patients with anal cancer treated by combined chemoradiation by use of helical tomotherapy from March 2007 to November 2008 were selected. With patients immobilized and positioned in place, megavoltage computed tomography (MVCT) scans were performed before each treatment and were automatically registered to planning CT scans. Patients were shifted per the registration data and treated. A total of 365 MVCT scans were analyzed. The primary site received a median dose of 55 Gy. To evaluate the potential dosimetric advantage(s) of IGRT, cases were replanned according to Radiation Therapy Oncology Group 0529, with and without adding recommended setup variations from the current study. RESULTS: Significant setup variations were observed throughout the course of RT. The standard deviations for systematic setup correction in the anterior-posterior (AP), lateral, and superior-inferior (SI) directions and roll rotation were 1.1, 3.6, and 3.2 mm, and 0.3°, respectively. The average random setup variations were 3.8, 5.5, and 2.9 mm, and 0.5°, respectively. Without daily IGRT, margins of 4.9, 11.1, and 8.5 mm in the AP, lateral, and SI directions would have been needed to ensure that the planning target volume (PTV) received ≥95% of the prescribed dose. Conversely, daily IGRT required no extra margins on PTV and resulted in a significant reduction of V15 and V45 of intestine and V10 of pelvic bone marrow. Favorable toxicities were observed, except for acute hematologic toxicity. CONCLUSIONS: Daily MVCT scans before each treatment can effectively detect setup variations and thereby reduce PTV margins in the treatment of anal cancer. The use of concurrent chemotherapy and IGRT provided favorable toxicities, except for acute hematologic toxicity.

Full-dose adjuvant postoperative radiation therapy for retroperitoneal sarcomas.

OBJECTIVES: To categorize sites of recurrence of retroperitoneal sarcomas (RPS) and correlate to clinical treatment volumes of postoperative radiation therapy (PORT) with or without intraoperative radiation therapy (IORT). METHODS: A retrospective review of patients with RPS who received PORT between 1990 and 2008 was done. Tumor recurrences were subdivided as local tumor bed, regional adjacent retroperitoneal fascial tissues, peritoneal diffuse seeding, and distant metastases. RESULTS: PORT was given to 33 patients, 20 of whom also received IORT. Local recurrences appeared in 4 (12%) cases. Regional recurrences appeared in 8 (26%) cases, including 5 with in-field recurrence and 3 with edge-of-field recurrence. Edge-of-field recurrences developed in 3 of 11 (27%) patients whose clinical presentation was local recurrence compared with none of 20 patients whose clinical presentation was a primary tumor (P=0.037). Late grades 3 to 4 gastrointestinal toxicities appeared in 1 of 10 (10%) patients who received intensity-modulated radiation therapy (IMRT) with a minimum 15-month follow-up compared with 4 of 15 (27%) patients who received standard RT. CONCLUSIONS: Use of techniques such as IORT and IMRT can deliver a dose of approximately 60 Gy to the tumor bed and 44 to 51 Gy to the surrounding retroperitoneal fascial planes. Acute and late gastrointestinal toxicities were less frequent with IMRT compared with conventional PORT with IORT. These results may provide the basis for comparison of various adjuvant therapy strategies for RPS. As radiation therapy is a loco-regional treatment, results should be reported by tumor recurrence subtypes of local, regional, peritoneal, and distant.

Malignant phyllodes tumor of the breast: local control rates with surgery alone.

PURPOSE: Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. METHODS AND MATERIALS: We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. RESULTS: Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). CONCLUSIONS: Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.

Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution.

We compare different radiotherapy techniques-helical tomotherapy (tomotherapy), step-and-shoot IMRT (IMRT), and 3-dimensional conformal radiotherapy (3DCRT)-for patients with mid-distal esophageal carcinoma on the basis of dosimetric analysis. Six patients with locally advanced mid-distal esophageal carcinoma were treated with neoadjuvant chemoradiation followed by surgery. Radiotherapy included 50 Gy to gross planning target volume (PTV) and 45 Gy to elective PTV in 25 fractions. Tomotherapy, IMRT, and 3DCRT plans were generated. Dose-volume histograms (DVHs), homogeneity index (HI), volumes of lung receiving more than 10, 15, or 20 Gy (V(10), V(15), V(20)), and volumes of heart receiving more than 30 or 45 Gy (V(30), V(45)) were determined. Statistical analysis was performed by paired t-tests. By isodose distributions and DVHs, tomotherapy plans showed sharper dose gradients, more conformal coverage, and better HI for both gross and elective PTVs compared with IMRT or 3DCRT plans. Mean V(20) of lung was significantly reduced in tomotherapy plans. However, tomotherapy and IMRT plans resulted in larger V(10) of lung compared to 3DCRT plans. The heart was significantly spared in tomotherapy and IMRT plans compared to 3DCRT plans in terms of V(30) and V(45). We conclude that tomotherapy plans are superior in terms of target conformity, dose homogeneity, and V(20) of lung.

Setup variations in radiotherapy of esophageal cancer: evaluation by daily megavoltage computed tomographic localization.

PURPOSE: To use pretreatment megavoltage computed tomography (MVCT) scans to evaluate setup variations in anterior-posterior (AP), lateral, and superior-inferior (SI) directions and rotational variations, including pitch, roll, and yaw, for esophageal cancer patients treated with helical tomotherapy. METHODS AND MATERIALS: Ten patients with locally advanced esophageal cancer treated by combined chemoradiation using helical tomotherapy were selected. After patients were positioned using their skin tattoos/marks, MVCT scans were performed before every treatment and automatically registered to planning kilovoltage CT scans according to bony landmarks. Image registration data were used to adjust patient setups before treatment. A total of 250 MVCT scans were analyzed. Correlations between setup variations and body habitus, including height, weight, relative weight change, body surface area, and patient age, were evaluated. RESULTS: The standard deviations for systematic setup corrections in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 1.5, 3.7, and 4.8 mm and 0.5 degrees, 1.2 degrees, and 0.8 degrees, respectively. The appropriate averages of random setup variations in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 2.9, 5.2, and 4.4 mm, and 1.0 degrees, 1.2 degrees, and 1.1 degrees, respectively. Setup variations were stable throughout the entire course of radiotherapy in all three translational and three rotational displacements, with little change in magnitude. No significant correlations were found between setup variations and body habitus variables. CONCLUSIONS: Daily MVCT scans before each treatment can effectively detect setup errors and thereby reduce planning target volume (PTV) margins. This will reduce radiation dose to critical organs and may translate into lower treatment-related toxicities.

Pitch, roll, and yaw variations in patient positioning.

PURPOSE: To use pretreatment megavoltage-computed tomography (MVCT) scans to evaluate positioning variations in pitch, roll, and yaw for patients treated with helical tomotherapy. METHODS AND MATERIALS: Twenty prostate and 15 head-and-neck cancer patients were selected. Pretreatment MVCT scans were performed before every treatment fraction and automatically registered to planning kilovoltage CT (KVCT) scans by bony landmarks. Image registration data were used to adjust patient setups before treatment. Corrections for pitch, roll, and yaw were recorded after bone registration, and data from fractions 1-5 and 16-20 were used to analyze mean rotational corrections. RESULTS: For prostate patients, the means and standard deviations (in degrees) for pitch, roll, and yaw corrections were -0.60 +/- 1.42, 0.66 +/- 1.22, and -0.33 +/- 0.83. In head-and-neck patients, the means and standard deviations (in degrees) were -0.24 +/- 1.19, -0.12 +/- 1.53, and 0.25 +/- 1.42 for pitch, roll, and yaw, respectively. No significant difference in rotational variations was observed between Weeks 1 and 4 of treatment. Head-and-neck patients had significantly smaller pitch variation, but significantly larger yaw variation, than prostate patients. No difference was found in roll corrections between the two groups. Overall, 96.6% of the rotational corrections were less than 4 degrees. CONCLUSIONS: The initial rotational setup errors for prostate and head-and-neck patients were all small in magnitude, statistically significant, but did not vary considerably during the course of radiotherapy. The data are relevant to couch hardware design for correcting rotational setup variations. There should be no theoretical difference between these data and data collected using cone beam KVCT on conventional linacs.

Dosimetric comparison of helical tomotherapy treatment and step-and-shoot intensity-modulated radiotherapy of retroperitoneal sarcoma.

PURPOSE: To compare step-and-shoot intensity-modulated radiation therapy (SAS-IMRT) and helical tomotherapy (Tomo) dosimetry plans for patients who have received adjuvant radiation therapy for retroperitoneal sarcomas (RSTS). METHODS AND MATERIALS: A retrospective review was performed for seven patients who received either SAS-IMRT or Tomo as adjuvant radiation therapy for RSTS. In each case, a treatment plan of the other modality was generated so that SAS-IMRT and Tomo could be compared. RESULTS: The average percentage of clinical target volume (CTV) that received less than the prescription dose was 1.4% for Tomo compared to 3.8% for SAS-IMRT. Both SAS-IMRT and Tomo plans provided comparable and significant reductions in volume of small bowel receiving greater than 45 Gy compared to simple opposing standard radiation fields. For the ipsilateral kidney, Tomo significantly reduced the volume of kidney that received at least 15 Gy (average 22% for Tomo vs. 56% for SAS-IMRT). CONCLUSION: Both SAS-IMRT and Tomo can encompass the large CTV often required for patients with RSTS, although Tomo provides superior dose uniformity. Both SAS-IMRT and Tomo can minimize the volume of small bowel receiving greater than 45 Gy. Tomo was superior to SAS-IMRT in minimizing the volume of ipsilateral kidney irradiated to greater than 15 Gy when the CTV is adjacent to a kidney. Dose escalation and target margin expansion may thus become realistic possibilities.

Dosimetric comparisons of helical tomotherapy treatment plans and step-and-shoot intensity-modulated radiosurgery treatment plans in intracranial stereotactic radiosurgery.

PURPOSE: To evaluate dose conformity, dose homogeneity, and dose gradient in helical tomotherapy treatment plans for stereotactic radiosurgery, and compare results with step-and-shoot intensity-modulated radiosurgery (IMRS) treatment plans. METHODS AND MATERIALS: Sixteen patients were selected with a mean tumor size of 14.65 +/- 11.2 cm3. Original step-and-shoot IMRS treatment plans used coplanar fields because of the constraint of the beam stopper. Retrospective step-and-shoot IMRS plans were generated using noncoplanar fields. Helical tomotherapy treatment plans were generated using the tomotherapy planning station. Dose conformity index, dose gradient score index, and homogeneity index were used in plan intercomparisons. RESULTS: Noncoplanar IMRS plans increased dose conformity and dose gradient, but not dose homogeneity, compared with coplanar IMRS plans. Tomotherapy plans increased dose conformity and dose gradient, yet increased dose heterogeneity compared with noncoplanar IMRS plans. The average dose conformity index values were 1.53 +/- 0.38, 1.35 +/- 0.15, and 1.26 +/- 0.10 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The average dose homogeneity index values were 1.15 +/- 0.05, 1.13 +/- 0.04, and 1.18 +/- 0.09 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The mean dose gradient score index values were 1.37 +/- 19.08, 22.32 +/- 19.20, and 43.28 +/- 13.78 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The mean treatment time in tomotherapy was 42 +/- 16 min. CONCLUSIONS: We were able to achieve better dose conformity and dose gradient in tomotherapy plans compared with step-and-shoot IMRS plans for intracranial stereotactic radiosurgery. However, tomotherapy treatment time was significantly larger than that in step-and-shoot IMRS.

Organ sparing by conformal avoidance intensity-modulated radiation therapy for anal cancer: dosimetric evaluation of coverage of pelvis and inguinal/femoral nodes.

PURPOSE: To describe a novel and straightforward conformal avoidance intensity-modulated radiation therapy (IMRT) technique for coverage of pelvis and inguinal/femoral nodes and to compare the dosimetry of the new method with that of other traditional methods of radiation treatment. METHODS AND MATERIALS: Data of 2 patients with anal cancer were used as example cases to illustrate details and advantages of conformal avoidance IMRT technique. Conventional photons with enface electrons design was created first, thereby providing "outermost boundaries" defined as planning target volume (PTV) for subsequent conformal avoidance IMRT design. Organs at risk (OARs), including femoral head and neck and external genitalia, were contoured as conformal avoidance structures. A step-and-shoot inverse IMRT planning was subsequently generated. For dosimetric comparison, a recently published technique by modified segmental boost was also generated. These treatment techniques were evaluated by dose-volume histogram (DVH) of PTV and OARs. Dose profiles at four different depths from each treatment planning were generated for comparison. RESULTS: The DVH of PTV showed that coverage of the PTV was comparable among three treatment techniques. Percent volume of PTV receiving more than 90% prescription dose was in the range 94-98% for the three treatment techniques, and all had only 0-2% of PTV receiving more than 110% of prescription dose. The DVH of OARs confirmed that both femoral head and neck and external genitalia could be spared well by conformal avoidance IMRT as compared with the other two techniques. Although greater inhomogeneity of dose distribution within the PTV was noted by conformal avoidance IMRT technique, as shown by dose profiles at four different depths, the maximum doses at different depths were less than 115%, which was comparable to those planned by modified segmental boost technique. Planning by photons and enface electrons technique, however, showed a greater dose variation up to 134% of the prescription dose at 1.5 cm depth along photon-electron match-line. CONCLUSIONS: To cover pelvis and inguinal/femoral nodes, conformal avoidance IMRT is technically simple to simulate, plan, and execute. Dosimetric study has demonstrated that it achieves comparable PTV coverage compared with other approaches while at the same time significantly sparing the surrounding OARs.

Impact of intraoperative radiation on postoperative and disease-specific outcome after pancreatoduodenectomy for adenocarcinoma: a propensity score analysis.

For periampullary cancer,intraoperative radiation therapy (IORT) administered to the site with the highest locoregional recurrence risk carries the rationale to improve tumor control. An IORT effect on survival remains unclear. IORT impact on postoperative outcomes after pancreatectomy for adenocarcinoma was analyzed, with a specific attempt to correct for the nonrandom IORT treatment assignment, and to account for treatment group imbalances in the interpretation of outcome differences. A propensity-score-adjusted analysis, based on variable selection by logistic regression, was used to rebalance treatments. Between 1989 and 1999, 61 patients underwent partial or total pancreatectomy for a primary periampullary adenocarcinoma at the City of Hope National Medical Center. Diagnoses included pancreatic (n = 36), duodenal (n = 11), ampullary (n = 10), and bile duct cancer (n = 4). Thirty patients received IORT to the resection area, with a median dose of 15 Gy (range: 10-20), followed by postoperative external beam radiation (n = 24). Mortality was 0%, the complication rate 61%. Of 33 patients with a documented recurrence, 6 had an isolated locoregional recurrence only (1 IORT versus 5 no IORT, = 0.05); the systemic recurrence pattern differed as well (IORT 94%, no IORT 67%; = 0.04). IORT had no significant impact on hospital stay (overall median: 17 days), disease-free survival (16 months), and overall survival (23 months) when adjusted for those most relevant variables reflecting IORT treatment group assignment propensity. After adjustment for relevant propensity factors, IORT was not linked to a significantly increased risk for complications, hospital stay, or survival hazard. The recurrence pattern may be affected in some patients, but systemic recurrences predominate. We continue to explore IORT in combination with systemic chemotherapy.

Intraoperative radiation therapy for patients with recurrent rectal and sigmoid colon cancer in previously irradiated fields.

A retrospective study evaluated 15 patients with pelvic recurrence of colorectal cancer in a previously irradiated region who received intraoperative radiation therapy (IORT) as part of salvage therapy. Total prior external beam radiation therapy (EBRT) doses ranged from 45 to 79.2 Gy. Tumor resection was accomplished in 14 patients, with an exenteration performed in seven. IORT dose was 15-20 Gy. Three patients received additional EBRT as a post-operative course of 25.2 Gy in 14 fractions. Actuarial 3-year local control rate was 25%. The 3-year overall survival rate was 29%. Patients with fixed and/or bulky pelvic tumors had a local control rate of 19% at 12 months and median overall survival of 9 months. Patients with less extensive clinical presentations of anastomotic non-fixed transmural recurrence, isolated pelvic node metastasis and rectal recurrence following local excision had a local control rate of 42% at 36 months and median survival of 43 months. We conclude that clinical presentation of recurrent disease is an important prognostic factor. The value of IORT may be limited to patients with less extensive clinical presentations.