Radiotherapy of MRI-detected involved internal mammary lymph nodes in breast cancer.

BACKGROUND: The internal mammary (IM) lymph node chain, along with the axillary nodal basin, is a first-echelon breast lymphatic draining site. A growing body of evidence supports irradiation of this region in node-positive breast cancer. This study evaluated the effectiveness of radiotherapy in treating magnetic resonance imaging (MRI)-detected abnormal IM lymph nodes in newly-diagnosed non-metastatic breast cancer. METHODS: A structured query was performed on an electronic institutional database to identify women with radiographic evidence of abnormal IM node(s) on breast MRI from 2005 to 2013. Manual review narrowed inclusion to patients with a primary diagnosis of non-metastatic breast cancer with abnormal IM node(s) based on pathologic size criteria and/or abnormal enhancement. RESULTS: Of the 7070 women who underwent pre-treatment MRI, 19 (0.3%) were identified on imaging to have a total of 25 abnormal pre-treatment IM lymph nodes, of which 96% were located in the first two intercostal spaces and 4% in the third space. A majority of the primary tumors were high-grade (94.7%) and hormone-receptor negative (73.7%), while 47.4% overexpressed HER-2/neu receptor. Axillary nodal disease was present in 89.5% of patients, while one patient had supraclavicular involvement. At a median follow-up of 38 months, 31.6% of patients had developed metastatic disease and 21.1% had died from their disease. Of the patients who received IM coverage, none had progressive disease within the IM lymph node chain. CONCLUSIONS: Radiologic evidence of pre-treatment abnormal IM chain lymph nodes was associated with advanced stage, high grade, and negative estrogen receptor status. The majority of positive lymph nodes were located within the first two intercostal spaces, while none were below the third. Radiation of the IM chain in combination with modern systemic therapy was effective in achieving locoregional control without surgical resection in this cohort of patients.

Intraoperative radiation therapy techniques and options for breast cancer.

Intraoperative radiation therapy (IORT) applied to peri-tumoral tissue can play a significant role in preventing breast cancer recurrence. Approximately 80-100% of breast cancer recurrences occur at the tumor bed, thus restricting radiation to the postoperative bed may be reasonable in a select group of patients. IORT can be delivered as a boost in addition to standard external beam radiotherapy, or as a primary form of treatment. IORT can be administered via electrons generated by a linear accelerator or by a system using low-energy x-rays. Potential advantages of IORT include improved cosmesis, shorter overall treatment time, radiobiological advantages, and ability to define the tumor bed by direct visualization during surgery assuring accurate delivery of radiotherapy. IORT alone can be considered for appropriate patients with early breast cancer who may not require whole-breast radiation therapy. This review discusses patient criteria and benefits, IORT's roots, radiobiological considerations, treatment options, and device categories.

Toxicity after external beam radiotherapy for prostate cancer: an analysis of late morbidity in men with diabetes mellitus.

OBJECTIVE: To investigate the influence of diabetes mellitus (DM) on late genitourinary (GU) and gastrointestinal (GI) toxicity in patients treated with external beam radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: A total of 626 men were treated with curative-intent RT for prostate cancer from 1988 to 2008. Using the National Comprehensive Cancer Network risk category, the patients were considered to have low-risk (30%), intermediate-risk (42%), or high-risk (28%) prostate cancer. The median radiation dose was 74 Gy; 45% received androgen deprivation therapy for a median of 4 months. Late GU and GI Radiation Therapy Oncology Group toxicity was recorded prospectively at each visit after external beam RT. The median follow-up period was 55 months. RESULTS: Of the 626 men, 102 (16%) had DM that was controlled by diet (8%), oral medications (52%), or insulin (39%). The patients with DM were more likely to receive intensity-modulated RT and androgen deprivation therapy and to have a shorter follow-up duration (P ≤.05 for all). Univariate analyses demonstrated that greater radiation dose, baseline urinary dysfunction, intensity-modulated RT, and DM were associated with grade 2 or greater GU toxicity, and transurethral resection of the prostate and DM were associated with grade 3 or greater GU toxicity. In addition, androgen deprivation therapy use, age ≥70 years, and anticoagulation were associated with grade 2 or greater GI toxicity, and age ≥70 years and anticoagulation were associated with grade 3 or greater GI toxicity. The multivariate analyses for late toxicity demonstrated a greater risk of grade 2 or greater (relative risk 1.36, P = .10) and grade 3 or greater GU toxicity (relative risk 2.74, P = .04) with DM. CONCLUSION: A greater incidence of late GU toxicity was seen in patients with DM treated for prostate cancer. This relationship might be useful when considering the treatment of patients with DM, especially those receiving dose-escalated RT or with a history of transurethral resection of the prostate.

Brain metastasis in gestational trophoblastic neoplasia: an update.

OBJECTIVE: To update the treatment of brain metastases in gestational trophoblastic neoplasia (GTN) at the Brewer Trophoblastic Disease Center, comparing treatment and outcomes from 1995-2009 with those from 1962-1994. STUDY DESIGN: Thirty-seven patients with GTN who had brain metastases at presentation (25, 68%) or who developed brain metastases during treatment (12, 32%) were treated with chemotherapy and brain irradiation at the Brewer Center between 1962 and 2009 (26 prior to 1995 and 11 since 1995). Patients underwent whole brain irradiation (2400-4000 cGy in 200-300 cGy fractions prior to 1995, and 2400-3000 cGy in 200 cGy fractions since 1995) +/- radiosurgery. RESULTS: Of 11 patients with GTN treated for brain metastases since 1995, 7 (64%) are alive, and 4 died. Six (55%) of the 11 patients treated after 1995 were diagnosed with brain metastases during treatment, 3 (50%) of whom were cured, compared to 6 (23%) of the 26 patients treated before 1995, only 1 (17%) of whom was cured. CONCLUSION: The overall survival for all 37 patients with GTN who had brain metastases from 1962-2009 was 51% (19/37): 46% (12/26) before 1995 and 64% (7/11) after 1995. Survival was significantly influenced by symptoms at presentation: 100% (8/8) for asymptomatic patients versus 41% (7/17) for symptomatic patients (p=0.0005). No patient who died had uncontrolled brain metastases. In our experience, therefore, brain metastases in GTN are curable with a combination of systemic multiagent chemotherapy and whole brain irradiation.

Intracranial relapse rates and patterns, and survival trends following post-resection cavity radiosurgery for patients with single intracranial metastases.

The objective of this study is to evaluate the patterns of relapse and survival trends in patients with single brain metastases treated with post-operative adjuvant Gamma knife stereotactic radiosurgery (GKS) without whole brain radiotherapy (WBRT). Retrospective analysis of all consecutive patients who underwent GKS to the tumor cavity following resection of solitary brain metastasis was performed at a single institution. Between March 2001 and June 2010, 56 patients underwent GKS to the resection cavity following resection of intracranial metastases; no patient received pre- or post-operative WBRT as an adjuvant (salvage WBRT was permissible). The mean marginal dose was 17.1 Gy (range 14-20 Gy). The mean follow-up period was 24 months (range 3-99 months). Five patients (8.9%) had local recurrence in the immediate vicinity of the resection cavity, qualifying as "local failures", and 21 (37.5%) recurred at distant intracranial sites. Median intracranial recurrence free survival was 13 months. Median overall survival was 20.5 months. Salvage interventions were required in 26 patients, and included repeat radiosurgery in 17 patients, further surgery in two patients, and salvage WBRT in eight (14.3%; two of whom had also been locally salvaged with repeat radiosurgery) patients. As expected, avoidance of WBRT results in a high rate of intracranial failure (26/56 patients, 46%), even in well-selected patients with only single brain metastases. As anticipated, the majority of failures (21, 37.5%) are "distant intracranial", and in this well-selected cohort the local failure rate is low (5/56 patients, <9%). All patients failing intracranially (46%) are potential candidates for salvage therapies, but WBRT as salvage was utilized in only 14.3% of patients. The median intracranial relapse-free was 13 months and overall survival was 20.5 months.

Late rectal toxicity after prostate brachytherapy: influence of supplemental external beam radiation on dose-volume histogram analysis.

PURPOSE: To describe the rate of gastrointestinal (GI) toxicity after prostate brachytherapy and describe how external beam radiation therapy (EBRT) may influence the association of rectal dose-volume histogram (DVH) parameters with rectal toxicity. METHODS AND MATERIALS: One hundred ten patients with prostate cancer were treated with I-125 brachytherapy alone (n=62, 144 Gy) or as a boost (n=48, 108 Gy) after 45-Gy EBRT. CT-based dosimetry was performed a median of 29 days after implantation. GI toxicity was evaluated by Radiation Therapy Oncology Group criteria. Median followup was 41 months. RESULTS: Eleven patients developed Grade 2+GI toxicity. Men treated with EBRT had an increased risk of GI toxicity, with freedom from Grade 2+ toxicity of 82% vs. 91% for implant alone, but this difference was not statistically significant (p=0.3044). Of the DVH parameters analyzed, only the rectal volume receiving the prescription dose (rV(100)(%)) was associated with late Grade 2+GI toxicity. Men with rV(100%) >or= 0.05 cc had a 4-year freedom from Grade 2+ toxicity of 77% vs. 100% for those with an rV(100%) <0.05 cc (p=0.0248). However, this relationship was only significant for the subset of patients treated with EBRT, where men with rV(100%) >or= 0.05 cc had a 26% risk of Grade 2+ toxicity compared with 0% for rV(100%) <0.05 cc. Additional DVH parameters, including dose to the hottest 0.1 cc (p=0.0199), 1% (p=0.0086), and 3% (p=0.0043), were also associated with GI toxicity but only in men treated with EBRT. CONCLUSIONS: Supplemental EBRT may lower the threshold for rectal toxicity after prostate brachytherapy. Morbidity can be minimized by observing rectal constraints.

Interfractional variations in patient setup and anatomic change assessed by daily computed tomography.

PURPOSE: To analyze the interfractional variations in patient setup and anatomic changes at seven anatomic sites observed in image-guided radiotherapy. METHODS AND MATERIALS: A total of 152 patients treated at seven anatomic sites using a Hi-Art helical tomotherapy system were analyzed. Daily tomotherapy megavoltage computed tomography images acquired before each treatment were fused to the planning kilovoltage computed tomography images to determine the daily setup errors and organ motions and deformations. The setup errors were corrected before treatment and were used, along with the organ motions, to determine the clinical target volume/planning target volume margins. The organ motions and deformations for 3 representative patient cases (pancreas, uterus, and soft-tissue sarcoma) and for 14 kidneys of 7 patients are presented. RESULTS: Interfractional setup errors in the skull, brain, and head and neck are significantly smaller than those in the chest, abdomen, pelvis, and extremities. These site-specific relationships are statistically significant. The margins required to account for these setup errors range from 3 to 8 mm for the seven sites. The margin to account for both setup errors and organ motions for kidney is 16 mm. Substantial interfractional anatomic changes were observed. For example, the pancreas moved up to +/-20 mm and volumes of the uterus and sarcoma varied