Partial-Length Treatment With Brachytherapy in Patients With Endometrial Cancer With High-Risk Features Is as Effective as Full-Length Vaginal Brachytherapy but With Reduced Toxicity.

PURPOSE: Full-length vaginal (FLV) brachytherapy for patients with endometrial cancer and high-risk features should be considered as per the American Brachytherapy Society to reduce distal vaginal recurrence in patients with endometrial cancers with papillary serous/clear cell histologies, grade 3 status, or extensive lymphovascular invasion. We sought to investigate this patient population and report outcomes of treatment with high-dose-rate (HDR) brachytherapy in women treated with FLV brachytherapy versus partial-length vaginal (PLV) brachytherapy. METHODS AND MATERIALS: With institutional review board approval, we identified patients with endometrial cancer meeting American Brachytherapy Society criteria of high-risk features treated with adjuvant HDR between 2004 and 2010. HDR doses were 21Gy in 3 fractions delivered to either the full-length or partial-length vagina. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group scale and Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer grading, respectfully. Vaginal recurrences were assessed by physical examination and pap smears. Statistical analyses were performed using SPSS version 23 software. RESULTS: Of 240 patients treated with HDR brachytherapy, 121 were treated with FLV brachytherapy, and 119, with PLV brachytherapy. The median follow-up was 9.5 years (range, 8-11 years) for FLV patients and 8.5 years (range, 7-10 years) for PLV patients; 0% of patients had vaginal recurrences, and 1.4% and 0.9% had proximal vaginal recurrences, respectively (P = .54). All patients treated with FLV brachytherapy developed grade 3 mucositis of the lower vagina/introitus (P < .0001) and had increased analgesics use compared with those treated with PLV brachytherapy (P < .0001). In total, 23% of patients treated with FLV brachytherapy developed grade 3 stenosis of the lower vagina/introitus, in contrast to 0% of patients treated with PLV brachytherapy (P < .0001). CONCLUSIONS: PLV brachytherapy is as effective as FLV brachytherapy in reducing local recurrence and causes a significantly lower incidence of acute and late toxicities. The results of this study caution radiation oncologists regarding the careful use of FLV brachytherapy in patients with endometrial cancer and high-risk features.

Dosimetric differences between cesium-131 and iodine-125 brachytherapy for the treatment of resected brain metastases.

PURPOSE: To compare treatment plans and evaluate dosimetric characteristics of permanent cesium-131 (131Cs) vs. iodine-125 (125I) implants used in brain brachytherapy. MATERIAL AND METHODS: Twenty-four patients with 131Cs implants from a prospective phase I/II trial were re-planned with 125I implants. In order to evaluate the volume of brain tissue exposed to radiation therapy (RT), the dose volume histogram was generated for both radioisotopes. To evaluate the dosimetric differences of the two radioisotopes we compared homogeneity (HI) and conformity indices (CI), and dose covering 100% (D100), 90% (D90), 80% (D80), and 50% (D50) of the clinical target volume (CTV). RESULTS: At the 100%, 90%, 80%, and 50% isodose lines, the 131Cs plans exposed less mean volume of brain tissue than the 125I plans (p < 0.001). The D100, D90, D80, and D50 were smaller for 131Cs (p < 0.001). The HI and CI for 131Cs vs. 125I were 19.71 vs. 29.04 and 1.31 vs. 1.92, respectively (p < 0.001). CONCLUSIONS: Compared to 125I, 131Cs exposed smaller volumes of brain tissue to equivalent doses of radiation and delivered lower radiation doses to equivalent volumes of the CTV. 131Cs exhibited a higher HI, indicating increased uniformity of doses within the CTV. Lastly, 131Cs presented a CI closer to 1, indicating that the total volume receiving the prescription dose was closer to the desired CTV volume. These results suggest that 131Cs is dosimetrically superior to 125I and may explain the reason for the 0% incidence of radiation necrosis (RN) in our previously published prospective study using 131Cs.

A matched-pair analysis of clinical outcomes after intracavitary cesium-131 brachytherapy versus stereotactic radiosurgery for resected brain metastases.

OBJECTIVE: Adjuvant radiation therapy (RT), such as cesium-131 (Cs-131) brachytherapy or stereotactic radiosurgery (SRS), reduces local recurrence (LR) of brain metastases (BM). However, SRS is less efficacious for large cavities, and the delay between surgery and SRS may permit tumor repopulation. Cs-131 has demonstrated improved local control, with reduced radiation necrosis (RN) compared to SRS. This study represents the first comparison of outcomes between Cs-131 brachytherapy and SRS for resected BM. METHODS: Patients with BM treated with Cs-131 and SRS following gross-total resection were retrospectively identified. Thirty patients who underwent Cs-131 brachytherapy were compared to 60 controls who received SRS. Controls were selected from a larger cohort to match the patients treated with Cs-131 in a 2:1 ratio according to tumor size, histology, performance status, and recursive partitioning analysis class. Overall survival (OS), LR, regional recurrence, distant recurrence (DR), and RN were compared. RESULTS: With a median follow-up of 17.5 months for Cs-131-treated and 13.0 months for SRS-treated patients, the LR rate was significantly lower with brachytherapy; 10% for the Cs-131 cohort compared to 28.3% for SRS patients (OR 0.281, 95% CI 0.082-0.949; p = 0.049). Rates of regional recurrence, DR, and OS did not differ significantly between the two cohorts. Kaplan-Meier analysis with log-rank testing showed a significantly higher likelihood of freedom from LR (p = 0.027) as well as DR (p = 0.018) after Cs-131 compared to SRS treatment (p = 0.027), but no difference in likelihood of OS (p = 0.093). Six (10.0%) patients who underwent SRS experienced RN compared to 1 (3.3%) patient who received Cs-131 (p = 0.417). CONCLUSIONS: Postresection patients with BM treated with Cs-131 brachytherapy were more likely to achieve local control compared to SRS-treated patients. This study provides preliminary evidence of the potential of Cs-131 to reduce LR following gross-total resection of single BM, with minimal toxicity, and suggests the need for a prospective study to address this question.

Placement of 131Cs permanent brachytherapy seeds in a large combined cavity of two resected brain metastases in one setting: case report and technical note.

Large brain metastases are presently treated with surgical resection and adjuvant radiotherapy. However, local control (LC) for large tumors decreases from over 90% to as low as 40% as the tumor/cavity increases. Intraoperative brachytherapy is one of the focal radiotherapy techniques, which offers a convenient option of starting radiation therapy immediately after resection of the tumor and shows at least an equivalent LC to external techniques. Our center has pioneered this treatment with a novel FDA-cleared cesium-131 (131Cs) radioisotope for the resected brain metastases, and published promising results of our prospective trial showing superior results from 131Cs application to the large tumors (90%). We report a 57-year-old male patient, with metastatic hypopharyngeal brain cancer. The patient presented with two metastases in the right frontal and right parietal lobes. Post-resection of these lesions resulted in a large total combined cavity diameter of 5.3 cm, which was implanted with 131Cs seeds. The patient tolerated the procedure well, with 100% local control and 0% radiation necrosis. This case is unique in demonstrating that the 131Cs isotope was not only a convenient option of treating two resected brain metastases in one setting, but also that this treatment option offered excellent long-term LC and minimal toxicity rates.

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme.

Introduction Patients with glioblastoma multiforme (GBM) over age 65 represent nearly half of those diagnosed per annum. They have a different tumor markers profile, physiologic reserve, and a median survival as low as three to four months. An optimal treatment strategy in older GBM patients remains undefined, with many patients receiving radiation in 30 treatments over six weeks, a regimen based on trials originally excluding patients over age 70. Recent studies have suggested reducing the number of treatments to 10-15 over two to three weeks with similar efficacy. We present an elderly population of patients treated with six radiation treatments. Methods After IRB approval, we reviewed the electronic medical records of 20 consecutive patients over the age 60 at diagnosis with GBM, treated with maximally safe neurosurgical resection, and adjuvant hypofractionated radiation (HFRT) and temozolomide (TMZ) between 2012 and 2015. HFRT was given every other weekday for two weeks, in a total of six fractions (6 × 6 Gy to contrast-enhancing tumor +5 mm and 6 × 4 Gy to fluid-attenuated inversion recovery (FLAIR) +2 cm) with concurrent TMZ (75 mg/m2 daily), followed by adjuvant TMZ (150-200 mg/m2 in 5/28 days). The response was assessed using the Macdonald and Revised Assessment in Neuro-Oncology (RANO) criteria, radiology reports, physician notes, and tumor board consensus notes. Descriptive statistics, overall survival (OS), progression-free survival (PFS), toxicity, and steroid use were calculated and compared to the historical controls of patients treated with a six-week radiation regimen of 60 Gy in 30 fractions with TMZ.   Results The median age at diagnosis was 70.5 years (range: 61 - 82 years). Median pre-radiation Karnofsky performance scale (KPS) was 60 (range: 40 - 90). The median preoperative maximum gross tumor diameter on MRI was 3.6 cm (range: 1.8 - 6 cm). Six patients (30%) had a gross total resection (GTR), eight (40%) had a subtotal resection (STR), and six (30%) had biopsy only. The median progression-free survival was five months (95% (confidence interval) CI: 2.8, 16.4) and median OS of 14 months (95% CI: 5.0, upper limit not estimable). Of the 19 patients tested for isocitrate dehydrogenase-1 (IDH), 100% were negative. Of the eight patients who had MGMT methylation status results, four (50%) were positive for O6-methylguanine-DNA methyltransferase (MGMT) methylation. In the 18 patients who completed radiation, the HFRT treatment was well tolerated without any Grade 3/4 acute toxicities. Conclusions The accelerated adjuvant course of HFRT with TMZ used for the elderly with GBM decreases radiation treatment days to six. It was well tolerated in patients over 60 years of age and provided similar OS, PFS, minimal toxicity, and decreased steroid usage compared to historical controls treated with six or even two to three weeks of radiotherapy.

Clinical Outcomes of Large Brain Metastases Treated With Neurosurgical Resection and Intraoperative Cesium-131 Brachytherapy: Results of a Prospective Trial.

PURPOSE: Studies on adjuvant stereotactic radiosurgery to the cavity of resected brain metastases have suggested that larger tumors (>2.0 cm) have greater rates of recurrence and radionecrosis (RN). The present study assessed the effect of permanent low-dose 131Cs brachytherapy on local control and RN in patients treated for large brain metastases. METHODS AND MATERIALS: After institutional review board approval, 42 patients with 46 metastases ≥2.0 cm in preoperative diameter were accrued to a prospective trial from 2010 to 2015. Patients underwent surgical resection with intraoperative placement of stranded 131Cs seeds as permanent volume implants in the resection cavity. The primary endpoint was local freedom from progression (FFP). Secondary endpoints included regional and distant FFP, overall survival (OS), and RN rate. Failures 5 to 20 mm from the cavity and dural-based failures were considered regional. A separate analysis was performed for metastases >3.0 cm. RESULTS: Of the 46 metastases, 18 were >3.0 cm in diameter. The median follow-up period was 11.9 months (range 0.6-51.9). The metastases had a median preoperative diameter of 3.0 cm (range 2.0-6.8). The local FFP rate was 100% for all tumor sizes. Regional recurrence developed in 3 of 46 lesions (7%), for a 1-year regional FFP rate of 89% (for tumors >3.0 cm, the FFP rate was 80%, 95% confidence interval 54%-100%). Distant recurrences were found in 19 of 46 lesions (41%), for a 1-year distant FFP rate of 52%. The median OS was 15.1 months, with a 1-year OS rate of 58%. Lesion size was not significantly associated with any endpoint on univariate or multivariate analysis. Radioresistant histologic features resulted in worse survival (P=.036). No cases of RN developed. CONCLUSIONS: Intraoperative 131Cs brachytherapy is a promising and effective therapy for large brain metastases requiring neurosurgical intervention, which can offer improved local control and lower rates of RN compared with stereotactic radiosurgery to the resection cavity.

Radiation Exposure and Safety Precautions Following 131Cs Brachytherapy in Patients with Brain Tumors.

Cesium-131 (Cs) brachytherapy is a safe and convenient treatment option for patients with resected brain tumors. This study prospectively analyzes radiation exposure in the patient population who were treated with a maximally safe neurosurgical resection and Cs brachytherapy. Following implantation, radiation dose rate measurements were taken at the surface, 35 cm, and 100 cm distances. Using the half-life of Cs (9.69 d), the dose rates were extrapolated at these distances over a period of time (t = 30 d). Data from dosimetry badges and rings worn by surgeons and radiation oncologists were collected and analyzed. Postoperatively, median dose rate was 0.2475 mSv h, 0.01 mSv h, and 0.001 mSv h and at 30 d post-implant, 0.0298 mSv h, 0.0012 mSv h, and 0.0001 mSv h at the surface, 35 cm, and 100 cm, respectively. All but one badge and ring measured a dose equivalent corresponding to ~0 mSv h, while 1 badge measured 0.02/0.02/0.02 mSv h. There was a significant correlation between the number of seeds implanted and dose rate at the surface (p = 0.0169). When stratified by the number of seeds: 4-15 seeds (n = 14) and 20-50 seeds (n = 4) had median dose rates of 0.1475 mSv h and 0.5565 mSv h, respectively (p = 0.0015). Using National Council on Radiation Protection guidelines, this study shows that dose equivalent from permanent Cs brachytherapy for the treatment of brain tumors is limited, and it maintains safe levels of exposure to family and medical personnel. Such information is critical knowledge for the neurosurgeons, radiation oncologists, nurses, hospital staff, and family as this method is gaining nationwide popularity.

Cesium-131 brachytherapy for recurrent brain metastases: durable salvage treatment for previously irradiated metastatic disease.

OBJECTIVE Managing patients whose intraparenchymal brain metastases recur after radiotherapy remains a challenge. Intraoperative cesium-131 (Cs-131) brachytherapy performed at the time of neurosurgical resection may represent an excellent salvage treatment option. The authors evaluated the outcomes of this novel treatment with permanent intraoperative Cs-131 brachytherapy. METHODS Thirteen patients with 15 metastases to the brain that recurred after stereotactic radiosurgery and/or whole brain radiotherapy were treated between 2010 and 2015. Stranded Cs-131 seeds were placed as a permanent volume implant. Prescription dose was 80 Gy at 5-mm depth from the resection cavity surface. The primary end point was resection cavity freedom from progression (FFP). Resection cavity freedom from progression (FFP), regional FFP, distant FFP, median survival, overall survival (OS), and toxicity were assessed. RESULTS The median duration of follow-up after salvage treatment was 5 months (range 0.5-18 months). The patients' median age was 64 years (range 51-74 years). The median resected tumor diameter was 2.9 cm (range 1.0-5.6 cm). The median number of seeds implanted was 19 (range 10-40), with a median activity per seed of 2.25 U (range 1.98-3.01 U) and median total activity of 39.6 U (range 20.0-95.2 U). The 1-year actuarial local FFP was 83.3%. The median OS was 7 months, and 1-year OS was 24.7%. Complications included infection (3), pseudomeningocele (1), seizure (1), and asymptomatic radionecrosis (RN) (1). CONCLUSIONS After failure of prior irradiation of brain metastases, re-irradiation with intraoperative Cs-131 brachytherapy implants provides durable local control and limits the risk of RN. The authors' initial experience demonstrates that this treatment approach is well tolerated and safe for patients with previously irradiated tumors after failure of more than 1 radiotherapy regimen and that it results in excellent response rates and minimal toxicity.

Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases.

OBJECT: Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS: After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS: The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS: The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Impact of a large breast separation on radiation dose delivery to the ipsilateral lung as result of respiratory motion quantified using free breathing and 4D CT-based planning in patients with locally advanced breast cancers: a potential for adverse clinical implications.

PURPOSE: We examined the effects of large breast separation (BS) on dosimetric and positional differences of radiation treatment plans of locally advanced breast cancers during a free-breathing respiratory cycle. MATERIALS AND METHODS: Computed tomography (CT) datasets of 18 patients were acquired using 3D, 4D-0% (end-inspiration), and 4D-50% (end-exhalation). BS was examined in relation to the positional and dosimetric changes to organs-at-risk (OAR). Based on dosimetric analysis of all three plans, we compared 4D-0% and 4D-50% for V5, V10, and V20 to 3D for heart and ipsilateral lung. Using 4D-0% and 4D-50% CTs, we recorded positional variations of the organs' centroid (centers of mass) and their effects on dosimetry. RESULTS: Median BS was 23.95 cm (range: 16.86-29.48 cm). There was a strong positive correlation between BS and dose to the ipsilateral lung for V5, V10, and V20, with the greatest linearity observed at V20 (R(2) = 0.23). At BS ≥ 27 cm, the dose increased during inspiration at V5, V10 , and V20 (P < 0.05). When comparing 4D and 3D for the heart, V5 and V10, decreased by average of 0.94% and 0.96% (P < 0.008), respectively. CONCLUSIONS: This study offers the first evidence of the impact of a large BS on radiation dose to the ipsilateral lung.

Role of isotope selection in long-term outcomes in patients with intermediate-risk prostate cancer treated with a combination of external beam radiotherapy and low-dose-rate interstitial brachytherapy.

OBJECTIVE: To examine the rates of long-term biochemical recurrence-free survival (BRFS) with respect to isotope in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) and brachytherapy. METHODS: A total of 242 consecutive patients with intermediate-risk prostate cancer were treated with iodine-125 ((125)I) or palladium-103 ((103)Pd) implants after EBRT (range 45.0-50.4 Gy) from 1996 to 2002. Of the 242 patients, 119 (49.2%) were treated with (125)I and 123 (50.8%) with (103)Pd. Multivariate Cox regression analysis was used to analyze BRFS, defined according to the Phoenix definition (prostate-specific antigen nadir plus 2 ng/mL) with respect to Gleason score, stage, pretreatment prostate-specific antigen level, and source selection. Late genitourinary/gastrointestinal toxicities were assessed using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. RESULTS: At a median follow-up of 10 years, the BRFS rate was 77.3%. A statistically significant difference was found in the 10-year BRFS rate between the (125)I- and (103)Pd-treated groups (82.7% and 70.6%, respectively; P = .001). The addition of hormonal therapy did not improve the 10-year BRFS rate (77.6%) compared with RT alone (77.1%; P = .22). However, a statistically significant difference in the BRFS rate was found with the addition of hormonal therapy to (103)Pd, improving the 10-year BRFS rate for (73.8%) compared with (103)Pd alone (69.1%; P = .008). On multivariate analysis, isotope type ((103)Pd vs (125)I), pretreatment prostate-specific antigen level >10 ng/mL, and greater tumor stage increased the risk of recurrence by 2.6-fold (P = .007), 5.9-fold (P < .0001), and 1.7-fold (P = .14), respectively. CONCLUSION: (125)I renders a superior rate of BRFS compared with (103)Pd when used with EBRT. Hormonal therapy does not provide additional benefit in patients with intermediate-risk prostate cancer treated with a combination of EBRT and brachytherapy, except for the addition of hormonal therapy to (103)Pd.

FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells.

Cranial irradiation is an effective treatment modality for both primary and metastatic brain tumors, yet it induces cognitive decline in a substantial number of patients. At present, there are no established methods for neuroprotection. Recent investigations have revealed a link between radiation-induced cognitive dysfunction and the loss of neural precursor cells in the hippocampus. Hence, identifying pharmacological agents, capable of protecting this cell population, is of interest. FTY720 (fingolimod), an FDA-approved oral drug for the treatment of multiple sclerosis, has been shown to promote the survival and differentiation of neural progenitors, as well as remyelination and repair after brain injury. In this study, we show that FTY720, used at nanomolar concentrations, is capable of increasing the viability and neurogenicity of irradiated neural stem cells from the hippocampus. In contrast, it does not provide radioprotection in a human breast cancer cell line and two glioma cell lines. These results suggest a potential therapeutic role for FTY720 as a neuroprotector during cranial irradiation. Further preclinical studies are warranted to evaluate this possibility.

Management of single malignant lung nodules in elderly patients (70 years or older) who are not candidates for lobectomy.

PURPOSE: The aim of this study was to evaluate and compare sublobar resection plus intraoperative seed implant (IOS) versus stereotactic body radiation therapy (SBRT) in patients with single malignant lung nodules in patients 70 years of age or older. MATERIALS AND METHODS: A retrospective chart review was performed and 47 patients with adequate information were selected for analysis. Thirty patients with single malignant lung nodules received SBRT. Seventeen patients received limited surgical resection plus radioactive seed implantation for solitary malignant lung nodules. Univariate statistical analysis showed a significant difference only for the age in the 2 groups: the mean age in the radioactive seed group, 78.8 years versus 76.1 years in the SBRT group (2-sided, P=0.05). RESULTS: There was high local control and minimal toxicity with either treatment modality and no significant difference among the 2 groups in terms of local control, survival, and toxicity. However, the distant failure was higher but not statistically significant in the SBRT group (9 of 30 patients in SBRT vs. 0 of 17 in IOS, P=0.1). CONCLUSIONS: Our study has shown excellent outcomes and limited toxicity in both IOS and SBRT for treatment of single malignant lung nodules in patients who are not candidates for lobectomy. However, a randomized trial is needed in this group of elderly patients to determine the most appropriate treatment.

Radiation therapy is well tolerated and produces excellent control rates in elderly patients with locally advanced head and neck cancers.

PURPOSE: Management of locally advanced head and neck cancer (LAHNC) in the elderly is challenging due to multiple co-morbidities, poor organ function and performance status. The aim of this study was to evaluate efficacy of radiation therapy (RT) in elderly patients, defined as 65 years and older, with high-risk LAHNC. MATERIALS AND METHODS: An IRB approved retrospective chart review of elderly patients was performed, of whom 73 patients were selected for analysis. The stages included were II/III-IV. Sites included were oropharynx, oral cavity, larynx, salivary gland, nasopharynx, nasal cavity, paranasal sinus, hypopharynx and unknown primary. RESULTS: Median age was 74 years. Thirty nine (53%) patients received concurrent chemotherapy. Median time to completion of RT was 53 days. Median external beam radiotherapy (EBRT) dose was 66 Gy. With a median follow-up of 24 months, overall local control (LC) was 80% and distant metastasis (DM) was 12%. Sixty patients (82%) were alive at the time of study. Two-year overall survival (OS) was 96% (95% CI=87%, 99%). Chemotherapy did not improve LC [80% (chemo) vs 79% (no chemo), p=0.88] or DM [11% (chemo) vs 14% (no chemo), p=0.73]. Interestingly, patients receiving RT using intensity-modulated radiation therapy (IMRT) had a significantly higher rate of LC vs three-dimensional conformal radiotherapy (3DCRT) (94% vs 68%, respectively, p=0.008). Grade 2/3 toxicity was seen in 70/73 (96%) patients while grade 4 toxicity was seen in three patients (4%). CONCLUSION: Elderly patients with LAHNC have high rates of LC and OS. Prospective studies can reveal more insight into this increasingly important clinical problem in elderly patients.

A single-dose conformal delivery of radiotherapy following osteoplasty : a novel approach to treatment of osteolytic metastasis in the setting of multiple myeloma.

Multiple myeloma (MM) is a very radiosensitive tumor. Fractionated external beam radiation, which takes approximately 2 weeks of therapy, is typically used to irradiate myelomatous bone lesions with the goal of palliation. However, traditional radiotherapeutic techniques are not only lengthy but they also involve a considerable amount of healthy bone marrow in the treatment ports, which may undermine the total marrow reserve of a patient. Because of the limited survival time of patients with metastatic cancer, novel treatment concepts shortening the overall treatment time is desirable. We present an innovative approach of delivering targeted intra-operative radiotherapy to a solitary osteolytic metastasis in one application, while sparing healthy bone marrow from radiation toxicity and substantially reducing the overall treatment time. A 78-year-old Caucasian male with MM, previously treated with chemotherapy, who was off chemotherapy for 2 years due to bone marrow suppression, presented with a solitary recurrence at the left anterior superior iliac spine of the left iliac wing as diagnosed by PET-CT scan. This lesion was treated with a minimally invasive osteoplasty and intra-operative brachytherapy with to a dose of 8 Gy delivered to the surgical cavity only, followed by injection of the bone cement into the cavity. Three months after the procedure, the area of treatment demonstrated no uptake on a follow-up PET-CT scan. At 1.5 years after this procedure, 100% local control continues to persist in the treated area, as evidenced on nuclear imaging. To our knowledge, this is the first case of using focal intra-operative brachytherapy confined to the area of the pelvis in a patient treated for a solitary metastasis from MM. The purpose of the article is to present a novel approach as a more convenient and focal treatment of bony lesions of MM.

Seroma is an expected consequence and not a complication of MammoSite brachytherapy.

Seroma has long been listed as a complication of MammoSite brachytherapy. Palpable abnormalities are clinically apparent months after treatment and a vast majority of patients demonstrate seroma formation in radiologic studies. We embarked on this study to evaluate the actual sonographic incidence and eventual sonographic resolution, possible contributing factors, cosmesis, pain, and local control associated with seroma formation after MammoSite partial breast irradiation (PBI). We investigated 160 patients who underwent MammoSite PBI from 2002 to 2006 of whom 100 patients had serial sonographic information. Clinical and tumor variables, infection, pain, and cosmesis were investigated. Dosimetric data including volume of balloon, dose at balloon surface, and at skin were analyzed. After a median follow-up of 36 months, the incidence of sonographically confirmed post-radiation seroma was 78% within the first 1 year following radiation and steadily decreased with time. The average size of a seroma cavity was 2.3 cm (range 0.6-6 cm) with a decline to an average of 1.4 cm after 1 year, with complete resolution in 65% of patients at 2 years. No statistically significant correlation was found between patient characteristics, tumor variables, and volumetric or dosimetric data for seroma formation. Excellent/good cosmetic scores were achieved in 94% of women with and 92% without seroma. Local control was equivalent between patients with and without seroma. Consecutive sonographic imaging reveals a high rate of seroma formation after MammoSite PBI, with resolution in 65% of patients by 2 years without intervention. Seroma formation does not prevent an excellent cosmetic result or alter local control.

Cesium-131 permanent seed brachytherapy: dosimetric evaluation and radiation exposure to surgeons, radiation oncologists, and staff.

PURPOSE: Cesium-131 ((131)Cs) radioactive seed is Food and Drug Administration approved for permanent seed implant for all cancers, including lung and head and neck (HN) cancers. We describe the first clinical report of (131)Cs dosimetry and exposure rates to treating physicians and staff. METHODS AND MATERIALS: Twenty-eight patients received (131)Cs implant for early stage lung and recurrent HN cancers. A nomogram was developed to calculate the number of seeds needed to cover the wedge line with the prescription dose (80 Gy). Final dosimetry was obtained after CT planning a few days following the surgical procedure. Radiation exposure to the treating physicians and staff was measured at the completion of the procedure. RESULTS: A nomogram was developed using the variseed software with source data from American Association of Physicists in Medicine TG-43 report. The total volume covered by the prescription isodose line of (131)Cs was measured and compared with (125)I. The prescription volume was smaller for (131)Cs. In addition, the exposure rate with (131)Cs was found to be acceptable. CONCLUSION: Our preliminary experience with (131)Cs lung and HN brachytherapy has been very encouraging with excellent dosimetric coverage and acceptable exposure to the treating physicians and staff.

Morphea as a consequence of accelerated partial breast irradiation.

Morphea is a localized form of scleroderma usually unaccompanied by the typical systemic stigmata that characterize progressive systemic scleroderma. It rarely manifests at the site of whole breast external-beam radiation therapy. We present an unusual case of radiation-induced morphea (RIM) that occurred after accelerated partial breast irradiation (APBI) using intracavitary Contura brachytherapy. A 65-year-old white woman was treated for stage IIA invasive ductal carcinoma of the left breast with APBI to a dose of 34 Gy in 3.4-Gy fractions twice daily over the course 5 days with intracavitary brachytherapy. At 1.5 years after completion of APBI, the patient developed an area of tenderness, erythema, and induration at the site of irradiation. A skin biopsy was consistent with morphea. To our knowledge, this is the first case of RIM confined to the area of APBI.

Chemotherapy significantly increases the risk of radiation pneumonitis in radiation therapy of advanced lung cancer.

INTRODUCTION: The reported rate of developing radiation pneumonitis (RP) in patients receiving definitive radiation therapy (RT) for lung cancer is 5% to 36%. However, this incidence is probably underreported because of the nonspecific symptoms of RP that may be erroneously attributed to another cardiovascular or respiratory disorder. The objective of this study was to evaluate the incidence of RP in lung cancer patients receiving RT or chemoradiation therapy. METHODS: Of the 110 patients that were reviewed, 86 were chosen for a retrospective analysis. A diagnosis of RP was made based on clinical assessment in the first 6 to 12 months after RT. Radiation pneumonitis was graded as per Radiation Therapy Oncology Group grading criteria. RESULTS: The incidence of developing grade 2 or higher RP was significantly associated with addition of chemotherapy. The incidence of RP in patients receiving chemotherapy was 62.7% (42/67) versus 15.8% (3/19) in patients receiving no chemotherapy (P < 0.001). However, there was no significant effect of the type or sequence of chemotherapy on the incidence of RP. The risk of developing RP is 5 times greater in patients receiving chemotherapy when compared with those not receiving this treatment (hazard ratio: 5.0; 95% confidence interval 1.5, 16.1). In addition, patients in age group 61 to 70 years had a significantly increased risk of developing RP compared with patients of age 60 or younger (hazard ratio: 3.0; 95% confidence interval: 1.4, 6.5). Histology and radiation dose were not significant factors in development of RP. CONCLUSION: The incidence of RP in patients receiving external-beam RT is significantly increased with addition of chemotherapy and 61 to 70 year age group.

Limited resection followed by intraoperative seed implantation is comparable to stereotactic body radiotherapy for solitary lung cancer.

BACKGROUND: The objective of this study was to compare the outcomes of patients who underwent wedge resection plus intraoperative brachytherapy versus patients who received stereotactic body radiotherapy (SBRT) for single malignant lung nodules. METHODS: A retrospective chart review included 55 patients who were treated for single lung nodules, and 47 of those patients who had adequate information were chosen for the current analysis. Twenty-five patients with single malignant lung nodules received SBRT. Twenty-two patients underwent limited surgical resection plus radioactive seed implantation for solitary malignant lung nodules. RESULTS: Univariate statistical analysis demonstrated a significance difference only for age in the 2 groups: The mean age in the radioactive seed group (66.6 years) was statistically significantly different from the mean of the age in the SBRT group (75.9 years; 2-sided P=.04). No significant differences were observed between the 2 groups in terms of local control, distant metastasis, survival, or toxicity. CONCLUSIONS: The current results demonstrated comparable efficacy in outcome and toxicity between surgical resection with radioactive seed implantation and SBRT for the treatment of single malignant lung nodules in patients who were not candidates for lobectomy/pneumonectomy.