Vladimir Valakh

Influence of concurrent anastrozole on acute and late side effects of whole breast radiotherapy.

Objectives: To retrospectively compare radiation toxicity in patients treated with concurrent anastrozole and whole breast irradiation versus women treated sequentially with whole breast irradiation followed by hormonal suppression. Methods: The records of 249 consecutive estrogen or progesterone receptor positive breast cancer patients treated with breast-conserving surgery and postoperative whole breast irradiation were reviewed. Of total, 57 patients (the concurrent anastrozole group) received concurrent anastrozole prior to and during radiotherapy. In 126 patients (the sequential group), adjuvant hormone suppression therapy (anastrozole, other aromatase inhibitors, or tamoxifen) was administered after the completion of breast irradiation. In 66, women either concurrent tamoxifen was given with radiation or the sequence of hormonal therapy was not known. These women were excluded from the analysis. Results: The frequency of acute grade 2 radiation dermatitis (24.6% in the concurrent anastrozole group vs. 20.6% in the sequential group; P = 0.55), grade 3 radiation dermatitis (8.8% vs. 7.1%; P = 0.77) and treatment interruptions due to skin reactions (14.0% vs. 11.2%; P = 0.69) did not differ between groups. The rates of clinically detectable breast fibrosis were not different (24.2% vs. 24.7%; P = 0.97). With a median follow-up of 28 months and 30.8 months, respectively, 1 local failure occurred in the concurrent anastrozole group and 5 in the sequential group. Conclusions: Anastrozole, administered concurrently with whole breast irradiation, did not increase acute or late morbidity when compared with sequential administration of radiation and hormonal suppression therapy.

Repeat stereotactic body radiation therapy for patients with pulmonary malignancies who had previously received SBRT to the same or an adjacent tumor site.

OBJECTIVES Retrospective analysis of patients with recurrences at or closely adjacent to the site of prior lung stereotactic body radiation therapy (SBRT) who received repeat SBRT. MATERIALS AND METHODS Nine patients with non-small cell lung cancer (n = 8) or oligometastatic colonic adenocarcinoma (n = 1) were treated with image-guided lung SBRT to a median of 60 Gy (range, 30-60) in a median of 3 fractions (3-5). Patients developed in-field relapse (n = 3) or recurrence adjacent (≤ 3.5 cm away) to the previous tumor location (n = 6) and received 2 nd lung SBRT to a median of 60 Gy. RESULTS Median follow-up after 2 nd SBRT was 22 months (4-40). All completed prescribed course of repeat SBRT and acute toxicity was limited. There was no grade >3 late toxicity. 3 (33.3%) patients developed Grade 3 late reactions: 2 pulmonary and 1 chest wall pain. Late pulmonary toxicity included 2 (22.2%) patients with Grade 3 and 3 (33.3%) with Grade 2. One patient (11.1%) had late Grade 3 and 1 (11.1%) Grade 2 chest wall pain. 1 (11.1%) developed Grade 2 late brachial plexopathy. No myelopathy was observed. Two patients developed progression of tumors treated by 2 nd SBRT. Local recurrence free survival and overall survival was 75% and 68.6%, respectively at 2 years. Relative volume of ipsilateral lung receiving 5 Gy (V5) and V10 were lower for 2 nd SBRT. CONCLUSION Repeat image-guided SBRT for patients with small peripheral recurrences was feasible and severe toxicity was not observed. Additional studies are needed to evaluate the safety and efficacy of lung reirradiation using 2 nd SBRT.

Mammary fat necrosis following radiotherapy in the conservative management of localized breast cancer: Does it matter?

PURPOSE Fat necrosis is a well-described and relatively common complication arising from post-lumpectomy irradiation of the breast, most commonly breast brachytherapy. We wish to assess the clinical significance of fat necrosis resulting from post-lumpectomy breast irradiation. METHODS We reviewed the literature to determine the overall incidence and significance of fat necrosis to determine whether or not fat necrosis poses a significant clinical problem. RESULTS Fat necrosis occurs in up to one-quarter of patients following post-lumpectomy breast irradiation. Only rarely is invasive intervention required however, it does significantly degrade the quality of all modalities of breast imaging. CONCLUSIONS Fat necrosis is a common complication of radiotherapy which rarely requires therapeutic intervention. However, post-therapeutic clinical imaging such as mammography, ultrasound and magnetic resonance imaging are affected which may result in additional diagnostic procedures up to and including biopsy.

Use of image-guided stereotactic body radiation therapy in lieu of intracavitary brachytherapy for the treatment of inoperable endometrial neoplasia

PURPOSE Retrospective analysis of patients with invasive endometrial neoplasia who were treated with external beam radiation therapy followed by stereotactic body radiation therapy (SBRT) boost because of the inability to undergo surgery or brachytherapy. METHODS AND MATERIALS We identified 11 women with stage I-III endometrial cancer with a median age of 78 years that were not candidates for hysterectomy or intracavitary brachytherapy secondary to comorbidities (91%) or refusal (9%). Eight patients were American Joint Committee on Cancer (AJCC) stage I (3 stage IA, 5 stage IB), and 3 patients were AJCC stage III. Patients were treated to a median of 4500 cGy at 180 cGy per fraction followed by SBRT boost (600 cGy per fraction×5). RESULTS The most common side effect was acute grade 1 gastrointestinal toxicity in 73% of patients, with no late toxicities observed. With a median follow-up of 10 months since SBRT, 5 patients (45%) experienced locoregional disease progression, with 3 patients (27%) succumbing to their malignancy. At 12 and 18 months from SBRT, the overall freedom from progression was 68% and 41%, respectively. Overall freedom from progression (FFP) was 100% for all patients with AJCC stage IA endometrial carcinoma, whereas it was 33% for stage IB at 18 months. The overall FFP was 100% for International Federation of Obstetrics and Gynecology grade 1 disease. The estimated overall survival was 57% at 18 months from diagnosis. CONCLUSION In this study, SBRT boost to the intact uterus was feasible, with encouragingly low rates of acute and late toxicity, and favorable disease control in patients with early-stage disease. Additional studies are needed to provide better insight into the best management of these clinically challenging cases.

Combination of IG-IMRT and permanent source prostate brachytherapy in patients with organ-confined prostate cancer: GU and GI toxicity and effect on erectile function

PURPOSE To assess toxicity outcomes of image-guided intensity-modulated radiation therapy (IG-IMRT) combined with permanent prostate seed implant in a cohort of patients with localized prostate cancer. METHODS AND MATERIALS A retrospective analysis was performed on 67 patients with the median pretreatment prostate-specific antigen level of 5.4. The Gleason score was less than 7 in 7 patients, 7 in 52 patients, and greater than 7 in 8 patients. The median followup was 28.2 months (range, 12-89.5 months). Treatment consisted of 45 (n=65) or 50.4 Gy (n=2) at 1.8 Gy/fraction of IG-IMRT to the prostate and seminal vesicles. Eight patients had simultaneous irradiation of pelvic lymph nodes to 45 (n=65) or 50.4 Gy (n=2). After IG-IMRT, patients received transperineal prostate implant boost with either (103)Pd (n=65, the prescribed D(90) of 100 Gy) or (125)I (n=2, D(90) of 110 Gy). Eleven patients received androgen deprivation therapy with radiotherapy. RESULTS Toxicity higher than Grade 3 was not observed. The combined incidence of acute and late Grade 3 genitourinary toxicity was 6%. The combined incidence of acute and late Grade 3 gastrointestinal toxicity was 3%. At least one episode of gastrointestinal bleeding on followup, which could be attributed to radiation, was recorded in 14.9% of patients. For patients achieving erections before radiation, the 3-year Kaplan-Meier potency preservation rate was 66.5%. CONCLUSIONS The early toxicity of the combination of IG-IMRT and low-dose rate brachytherapy boost in this study was favorable.

Reduction in Radiation-Induced Morbidity by Use of an Intercurrent Boost in the Management of Early-Stage Breast Cancer

PURPOSE Electron or photon boost immediately following whole-breast irradiation performed after conservation surgery for early-stage breast cancer is the accepted standard of care. This regimen frequently results in Grade III dermatitis, causing discomfort or treatment interruption. Herein, we compare patients treated with whole-breast irradiation followed by boost compared with a cohort with a planned intercurrent radiation boost. METHODS AND MATERIALS The records of 650 consecutive breast cancer patients treated at Allegheny General Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were 327 patients with T1 or T2 tumors treated with external beam radiotherapy postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT). The mean whole breast radiation dose in the conventionally treated group was 5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost. RESULTS The occurrence of Grade III dermatitis was significantly reduced in the WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%), as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median follow-up of 32 months and 27 months, respectively, no significant difference in local control was identified. CONCLUSIONS Patients treated with intercurrent boost developed less Grade III dermatitis and unplanned treatment interruptions with similar local control.

A comparison of outcomes for early oropharyngeal cancers treated with single-modality surgery versus radiotherapy

AIMS We retrospectively compared results of surgery alone (SX) or radiotherapy alone (RT) for early stage tonsil and base of tongue cancers. MATERIALS & METHODS Outcomes for 386 SX and 362 RT patients from Surveillance, Epidemiology and End RESULTS database were analyzed using propensity covariate adjusted and inverse probability weighting models. RESULTS With median follow-up of 71 months, unadjusted overall survival at 5 years was 66.1% for SX versus 50.2% for RT (p < 0.001). Unadjusted cancer-specific survival was 80.9% for SX versus 67.3% for RT (p < 0.001). In multivariate analysis, treatment modality maintained association with overall survival and cancer-specific survival. Inverse probability weighting-adjusted 5-year overall survival was 75.2% for SX versus 67.4% for RT (p = 0.002). Inverse probability weighting-adjusted cancer-specific survival was 86.0% for SX versus 77.4% for RT (p < 0.001). CONCLUSION Explanations for higher survival for SX include comorbidities, superiority of surgery and underascertainment of postoperative radiation in Surveillance, Epidemiology and End Results.

Implant R100 Predicts Rectal Bleeding in Prostate Cancer Patients Treated with IG-IMRT to 45 Gy and Pd-103 Implant

Purpose. To define factors associated with rectal bleeding in patients treated with IG-IMRT followed by Pd-103 seed implant. Methods and Materials. We retrospectively reviewed 61 prostate adenocarcinoma patients from 2002 to 2008. The majority (85.2%) were of NCCN intermediate risk category. All received IG-IMRT to the prostate and seminal vesicles followed by Pd-103 implant delivering a mean D90 of 100.7 Gy. Six patients received 45 Gy to the pelvic nodes and 10 received androgen deprivation. Results. Ten patients (16.4%) developed rectal bleeding: 4 were CTCAE v.3 grade 1, 5 were grade 2, and 1 was grade 3. By univariate analysis, age, stage, Gleason sum, PSA, hormonal therapy, pelvic radiation, postoperative prostate volume, D9, V100, individual source activity, total implanted activity per cm3, and duration of interval before implant did not impact rectal bleeding. Implant R100 was higher in patients with rectal bleeding: on average, 0.885 versus 0.396 cm3, , odds ratio of 2.26 per .5 cm3 (95% CI, 1.16–4.82). A trend for significance was seen for prostate V200 and total implanted activity. Conclusion. Higher implant R100 was associated with development of rectal bleeding in patients receiving IG-IMRT to 45 Gy followed by Pd-103 implant. Minimizing implant R100 may reduce the rate of rectal bleeding in similar patients.

4D-Video Usefulness For Tracking Respiration Motion in 4DCT Scans and Targeting Small Mobile Tumors

4DCT-based treatment plan, 4DCBCT-guided patient setup, and real-time tracking of target motion are essential for accurate stereotactic body radiotherapy (SBRT) of small mobile tumors. However, there is lack of correlation between 4DCT-4DCBCT data in phases of regular respiration cycles and the real-time monitored irregular respiration motion data. We are now proposing a real-time 4D video technique to synchronize respiration patterns in 4DCT, 4DCBCT, and real-time target motion during the dose delivery. Results of feasibility studies with sequential surface images on several patients and volunteers demonstrated the capability of detecting the breathing patterns by the movements of the frontal surfaces of the thorax and abdomen. The deep breathing concurs with larger thorax surface shifts of > 5-mm or tilt angles of > 2-degrees and longer respiratory cycles with periods of >6- seconds. Normal breathing usually has small thorax surface shifts of < 2-mm and angles of < 2-degrees but wide ranges of abdomen surface shifts from 2 to 30-mm and angles from 1 to 5 degrees. At free breathing conditions, we also find that patient respiration cycles and abdomen surface movements are frequently changed with time. More importantly, the personal respiration patterns are predictable with the dynamic volumetric curves determined by the abdomen and thorax surface movements. The surface movements and changes of surface covered volume can be correlated with dynamic volumetric changes in 4DCT and 4DCBCT scans. Thus, the 4D video technique is potentially useful for real-time tracking of small mobile targets in SBRT through synchronization with 4DCT or 4DCBCT.

External beam radiotherapy in the treatment of extensive vascular malformation of the lower extremity refractory to surgery and interventional embolisation therapy

This patient case-study represents the introduction of radiotherapy in the management of extra-cranial vascular malformations, a topic with virtually no supported literature before our case study. In those patients refractory to established therapies and facing the inevitability of mutilating amputation, radiotherapy may be a viable option to preserve the limb.