A Phase I Trial of a Methionine Restricted Diet with Concurrent Radiation Therapy.

Methionine is an essential amino acid critical for cell growth and survival. Preclinical evidence suggests a methionine restricted diet (MRD) sensitizes cancer to radiation therapy (RT), without significant adverse effects. However, this has never been evaluated in humans. The purpose of this pilot study was to evaluate the safety and feasibility of concurrent MRD with standard-of-care definitive RT in adults with any non-skin cancer malignancy. The MRD extended from 2 wk before RT initiation, through 2 wk beyond RT completion. The primary endpoint of safety was assessed as rate of grade 3 or higher acute and late toxicities. Feasibility was assessed with quantitative plasma amino acid panel every 2 wk during the MRD (target plasma methionine 13 µM). Nine patients were accrued over a two-year period, with five able to complete the treatment course. The trial was closed due to slow accrual and subjects' difficulty maintaining the diet. No grade 3 or higher adverse events were observed. Subjects' average methionine level was 18.8 µM during treatment, with average nadir 16.8 µM. These findings suggest the safety of concurrent MRD with RT, with toxicities comparable to those expected with RT alone. However, the diet was challenging, and unacceptable to most patients.

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking. METHODS AND MATERIALS: Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10-30 Gy in 1 fraction to 0-5 mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30 Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15-20 Gy and 30 Gy in 1 fraction marginal dose. RESULTS: For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30 Gy to retrospective SRS plans to standard 15-20 Gy and 30 Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis. CONCLUSIONS: Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30 Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study.

OBJECTIVE: The aim of the study was to characterize the impact of adjuvant therapy on survival in women with stage I/II uterine carcinosarcoma after primary surgery. METHODS: We reviewed records of 118 consecutively treated women with 2009 International Federation of Gynecology and Obstetrics stage I/II uterine carcinosarcoma who underwent hysterectomy between 1990 and 2014 at 4 academic institutions. Patients were categorized by adjuvant treatment group into observation, chemotherapy only, radiation only, and combined chemotherapy and radiation. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: Median follow-up was 28 months (range, 1-244 months). Lymphadenectomy was performed in 94 patients (80%). Postoperative management included observation (n = 37 [31%]), chemotherapy alone (n = 19 [16%]), radiation therapy (RT) alone (n = 24 [20%]), and combined RT and chemotherapy (n = 38 [32%]). Radiation therapy modality included vaginal brachytherapy in 22 patients, pelvic external beam RT in 21 patients, and combination in 19 patients. In 58% of women, chemotherapy consisted of carboplatin/paclitaxel. Median overall survival for all women was 97 months. On univariate analysis, adjuvant treatment group was associated with improved overall survival (hazard ratio [HR], 0.74; confidence interval [CI], 0.58-0.96; p = 0.02), freedom from vaginal recurrence (HR, 0.55; CI, 0.37-0.82]; p = 0.004), and freedom from any recurrence (HR, 0.70; CI, 0.54-0.92; p = 0.01). Pairwise comparisons demonstrated a significant benefit to chemoradiation over other adjuvant treatments. Adjuvant treatment group remained a significant covariate for all 3 end points on multivariate analysis as well. In addition, lymphadenectomy improved overall survival on multivariate analysis (HR, 0.24; CI, 0.09-0.61; p = 0.003). Of patients under observation only who had a recurrence, 8 (44%) of 18 had a recurrence in the vagina as the sole site of recurrence. By contrast, of women who received vaginal brachytherapy, significantly fewer had a recurrence in the vagina (1/42 [2.3%]; p < 0.003, log-rank test). CONCLUSIONS: In women with early-stage uterine carcinosarcoma, our data suggest superior survival end points with combined RT and chemotherapy. The frequency of vaginal recurrence suggests a role for incorporating vaginal brachytherapy in the adjuvant management of this disease.

Intraoperative Radiotherapy in Brain Malignancies: Indications and Outcomes in Primary and Metastatic Brain Tumors.

Despite the continued controversy over defining an optimal delivery mechanism, the critical role of adjuvant radiation in the management of surgically resected primary and metastatic brain tumors remains one of the universally accepted standards in neuro-oncology. Local disease control still ranks as a significant predictor of survival in both high-grade glioma and treated intracranial metastases with radiation treatment being essential in maximizing tumor control. As with the emergence and eventual acceptance of cranial stereotactic radiosurgery (SRS) following an era dominated by traditional radiotherapy, evidence to support the use of intraoperative radiotherapy (IORT) in brain tumors requiring surgical intervention continues to accumulate. While the clinical trial strategies in treating glioblastoma with IORT involve delivery of a boost of cavitary radiation prior to the planned standard external beam radiation, the use of IORT in metastatic disease offers the potential for dose escalation to the level needed for definitive adjuvant radiation, eliminating the need for additional episodes of care while providing local control equal or superior to that achieved with SRS in a single fraction. In this review, we explore the contemporary clinical data on IORT in the treatment of brain tumors along with a discussion of the unique dosimetric and radiobiological factors inherent in IORT that could account for favorable outcome data beyond those seen in other techniques.

Radiographic and Tumor Biomarker Response to Radiotherapy for Recurrent Granulosa Cell Tumor of the Ovary.

Granulosa cell tumors (GCTs) of the ovary are rare, comprising less than 5% of all malignant ovarian neoplasms. While generally considered indolent, GCTs have a tendency for metastasis and delayed relapse, with recurrence developing in 20%-50%. Recurrent or metastatic disease is associated with aggressive behavior and a poor prognosis, as nearly 70% of patients developing recurrence will eventually succumb to their disease. The optimal management of relapsed disease is controversial. Initial salvage therapy typically involves surgical debulking followed by cisplatin-based chemotherapy. Unfortunately, tumor responses are durable for less than half of patients treated with this regimen. Radiation therapy is an attractive option for providing rapid palliation and improving local control without the morbidity of additional surgery or chemotherapy. Here we describe a case of multiply recurrent, rapidly growing intraperitoneal GCT refractory to repeated surgical debulking and several lines of systemic therapy. The patient was treated with two courses of palliative radiotherapy and achieved rapid symptomatic relief, achieving over a 90% reduction in tumor volume. Serum concentration of inhibin B, often inappropriately elevated in patients with GCT, decreased by 98% following irradiation with no interim systemic therapy. At one-year follow-up, the patient has no evidence of radiographic or biochemical recurrence.

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION/BACKGROUND: This study assessed the safety and systemic (abscopal) response from the addition of local stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in patients with metastatic non-small cell lung cancer. PATIENTS/METHODS: Thirty-five patients with at least 2 sites of measurable disease on PET/CT received standard-of-care CPI immunotherapy alone (n = 19), or in combination with 4 cycles doublet carboplatin/pemetrexed chemotherapy (n = 16), and 3 to 5 fractions SBRT to a single extracranial target lesion between cycles 1 to 2 of the systemic therapy. Adverse events were assessed using CTCAE version 5.0. Best systemic objective response rate (ORR) was assessed using iRECIST criteria, excluding any irradiated lesion(s). Additional SBRT to a different target lesion was offered to patients who continued on immunotherapy with unconfirmed progressive disease or mixed response. RESULTS: Fifteen patients (44%) experienced 22 grade 1 to 2 toxicities potentially attributable to radiation, most commonly pneumonitis (n = 9) and fatigue (n = 6), and no grade 3 to 5 radiation-induced toxicities. Patients undergoing combined CPI-chemotherapy received a lower median biologically effective dose of SBRT than those undergoing CPI monotherapy (43.2 vs. 60Gy), but had a higher rate of radiation-induced toxicity (56% vs. 32%, P < .01). The best systemic ORR was 53%, with 20.5% stable disease and 26.5% progressive disease. Fifteen patients underwent a subsequent course of SBRT based on their response, among which 3 (20%) had progression-free intervals of 12, 16, and 10 months thereafter. CONCLUSIONS: Addition of SBRT to CPI immunotherapy (with/without chemotherapy) is safe. The favorable systemic response observed warrants further assessment with a randomized trial.

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies.

PURPOSE: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls. METHODS AND MATERIALS: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate. RESULTS: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01). CONCLUSIONS: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae.

Angiosarcoma following MammoSite partial breast irradiation.

Angiosarcoma is a rare tumor of endothelial origin which commonly arises in small blood or lymphatic vessels. Its development in the treated breast following adjuvant external beam radiation is also rare. To our knowledge, there are no reported cases in the literature or MammoSite registry which describe the occurrence of angiosarcoma in the treated breast following MammoSite brachytherapy. This is a case report of a 74 year old female who developed angiosarcoma 4 years after receiving MammoSite balloon brachytherapy following surgical resection of a T1mic N0 M0 infiltrating ductal carcinoma.

Preservation of immune function in cervical cancer patients during chemoradiation using a novel integrative approach.

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for (1) supporting cellular immunity, (2) improving mood and quality of life (QOL), and (3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4 ×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial assessments and blood sampling before chemoradiation at baseline, weeks 4 and 6. Multilevel regression analyses using orthogonal contrasts tested for differences between treatment conditions over time. HT patients had a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of RT and UC patients declined sharply during chemoradiation (group by time interaction: p = 0.018). HT patients showed greater decreases in two different indicators of depressed mood (CES-D depressed mood subscale and POMS depression scale) compared to RT and UC (group by time interactions: p<0.05). No between group differences were observed in QOL, treatment delay, or clinically-rated toxicities. HT may benefit cervical cancer patients by moderating effects of chemoradiation on depressed mood and cellular immunity. Effects of HT on toxicities, treatment delay, QOL, and fatigue were not observed. Long-term clinical implications of findings are not known.

Rethinking the Role of Radiation Therapy in the Management of Epithelial Ovarian Cancer.

: Radiation has been relegated to a palliative role in the management of epithelial ovarian cancer (EOC). Contemporary radiation techniques, including intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and image-guided radiation therapy, enable conformal treatment that controls local disease with minimal morbidity. Recent studies from multiple institutions support the role of radiation in the ablative treatment of oligometastatic disease and control of locally recurrent and metastatic disease. Effective local treatment with radiation complements the role of systemic therapy in the management of EOC; reduces symptoms and disease burden, and may contribute to a prolonged drug free interval.

Intraoperative Radiation Therapy Versus Whole Breast Radiation for Early-Stage Breast Cancer Treatment in Rural Appalachia.

BACKGROUND: Intraoperative radiation therapy (IORT) is an alternate accelerated form of radiation following breast-conserving surgery (BCS). Lack of data regarding long-term outcomes has limited adoption. We report our experience with IORT in patients undergoing BCS versus whole breast radiation therapy (WBRT). METHODS: Retrospective review of patients undergoing BCS with IORT versus WBRT (2012-2017). Inclusion: low grade, T1-2N0M0, estrogen receptor/progesterone receptor positive, and Her2-negative infiltrating ductal carcinomas. IORT was delivered as a single fraction of radiation (20 Gy) intraoperatively. Outcomes were compared using Fisher's test for discrete variables or Wilcoxon signed-rank test for continuous variables. Kaplan-Meier method was used to estimate disease-free survival (DFS). RESULTS: Fifty-one patients (44%) received IORT, and 66 (56%) received WBRT. There was no difference in age, tumor size, receptor status, or in-breast recurrence (1.9% vs 0%, all P > .05). Length of follow-up was longer in the WBRT group due to time to inception of IORT (mean ± SD: 44 ± 8.1 vs 73 ± 13 months, P < .001). There was no difference in DFS between the 2 groups (HR 2.5; P = .44). IORT patients experienced delay to BCS (mean ± SD: 38 ± 12.7 vs 27 ± 12.2 days, P < .001) likely due to coordination of care. Analysis demonstrated IORT patients would have traveled a mean distance of 20 miles to the closest WBRT center (range 1-70, miles) for a mean travel time of 31 minutes (range 4-90, minutes) per WBRT treatment. DISCUSSION: IORT produces noninferior oncologic outcomes and decreased skin toxicity compared with WBRT. It can be convenient for patients in rural regions with limited health care access.

Thromboembolic events in patients with cervical carcinoma: Incidence and effect on survival.

OBJECTIVES: The purpose of this study was to determine whether thromboembolic events (TE) in cervical cancer patients are associated with survival by comparing the survival of patients with and without thromboembolic events over a seven year period. METHODS: Utilizing a retrospective chart review we identified patients with any diagnosis of a TE, associated risk factors for TE development and overall survival. We also collected clinico-pathological data including stage, histology, height, weight, smoking history, radiation and chemotherapy treatment data and the temporal relationship of the development of TE to the time of cancer diagnosis. Data sources included the University of Iowa Hospitals and Clinics (UIHC) Tumor Registry and the UIHC Gynecologic Oncology Tumor Data Base as well as a search of UIHC medical record data bases using ICD-9 codes to initially identify all patients diagnosed with cervical carcinoma. RESULTS: In this study, the incidence of TE in cervical cancer patients was 11.7%. There was a clear and significant difference in survival between patients with and without TE. We identified an association between TE and stage, chemotherapy, brachytherapy, and radiation therapy. CONCLUSIONS: The major findings of our study are a significant incidence of thromboembolism in patients with cervical cancer, and a significant decrease in survival in patients who experience thromboembolism at presentation or during treatment. Deaths in these patients were overwhelmingly related to progressive cancer rather than the TE itself, suggesting that this adverse prognostic event may be related to aggressive tumor biology.

The Lack of Consensus of International Contouring Guidelines for the Dorsal Border of the Chest Wall Clinical Target Volume: What is the Impact on Organs at Risk and Relationships to Patterns of Recurrence in the Modern Era?

PURPOSE: Variation exists in cooperative group recommendations for the dorsal border for the chest wall clinical target volume (CTV). We aimed to quantify the impact of this variation on doses to critical organs and examine patterns of chest wall recurrence relative to the pectoralis muscle. METHODS AND MATERIALS: We retrospectively assessed patterns of chest wall recurrence quantified to the recommended CTV borders for women treated between 2005 and 2017. We compared treatment plans for 5 women who were treated with left postmastectomy radiation therapy, with the chest wall contoured using varying dorsal borders for CTV: (1) Anterior pleural surface (Radiation Therapy Oncology Group), (2) anterior surface of pectoralis major (European Society for Radiotherapy and Oncology), and (3) anterior rib surface (institutional practice). Treatment plans were generated for 50 Gy in 25 fractions. Doses to organs-at-risk were compared using paired-sample t tests. RESULTS: Institutional patterns of chest wall recurrence were 64.7% skin and subcutaneous tissue, 23.5% both anterior to and between the pectoralis muscles, and 11.8% isolated to the tissue between the pectoralis major and minor. No chest wall recurrences were noted deep to pectoralis minor. When comparing the plans generated per the Radiation Therapy Oncology Group versus European Society for Radiotherapy and Oncology contouring guidelines, the mean lung V20Gy, heart mean dose, and left anterior descending artery mean dose were 33.5% versus 29.4% (P < .01), 5.2 Gy versus 3.2Gy (P = .02), and 27.3Gy versus 17.8Gy (P = .04), respectively. CONCLUSIONS: The recommended variations in the dorsal chest wall CTV border have significant impact on doses to the heart and lungs. Although our study was limited by small numbers, our institutional patterns of recurrence would support a more anterior dorsal border for the chest wall CTV consistent with older literature.

Improving quality of care and timely access to radiation therapy for patients with invasive cervical cancer at the National Cancer Institute Paraguay.

The purpose of this report is to describe the interventions implemented between 2012 and 2017 at the National Cancer Institute Paraguay (NCI Paraguay) to improve treatment quality and efficiency for patients with cervical cancer, with an emphasis on radiation quality and access. The NCI Paraguay requested collaboration with Health Volunteers Overseas (HVO), an international volunteer organization, to improve the care of patients with cervical cancer. This report is based on site visits to NCI Paraguay by HVO volunteers in 2012, 2013, and 2016, with a follow-up report from the site in 2017. During the study period, increased access to external beam radiation and brachytherapy led to a decrease in wait time to start radiation from 2 to 3 months to 4-6 weeks. The center transitioned from 2-dimensional (2D) to 3-D planning and was able to offer concurrent chemotherapy and radiation, including brachytherapy, to patients with locally advanced cervical cancer. Based on the American Society of Clinical Oncology's resource-stratified clinical guidelines, from 2012 to 2017, the practice transitioned from a "basic setting" to an "enhanced setting".

Prognostic factors in breast cancer patients evaluated by positron-emission tomography/computed tomography before neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is a significant modality in breast cancer therapy. We sought to characterize prognostic factors in patients scheduled for NAC who had a pretreatment positron-emission tomography paired with diagnostic quality contrast-enhanced computed tomography (CT) (positron-emission tomography/CT [PET/CT]). A total of 118 breast cancer patients were analyzed through chart review who underwent pretreatment PET/CT imaging and received NAC from 2008 to 2014. We collected information on molecular markers, PET/CT, pathologic complete response (pCR), survival, and disease status. Pretreatment standard uptake value (SUV) max of the primary breast tumor showed no relationship to pCR; however, there was a statistically significant relationship with relapse-free survival (RFS) using univariate cox regression (P = 0.03, odds ratio (OR) = 1.06 [1.01-1.12]) with comparable findings observed with overall survival (OS). Multivariate analysis revealed SUV max to be significantly correlated with shortened OS (P = 0.022, OR = 1.08 [1.01-1.16]), with a similar trend reported for RFS. By pathological subtype, this correlation was the strongest within hormone receptor (HR+)/human epidermal growth factor receptor 2 (HER2-) tumors. In addition, Kaplan-Meier estimates demonstrated a significant difference between the RFS of triple-negative tumors and HER2 positive tumors (P = 0.001). Interestingly, within this cohort, multivariate Cox regression analysis showed HER2 positivity to be associated with favorable outcome (P = 0.04, HR = 0.22 [0.05-0.94]). These findings demonstrate a significant association between SUV max of HR+/HER2-- tumors and relapse-free and OS. Furthermore, highlighted here is the favorable survival in the once classically aggressive HER2+ breast cancer subgroup.

Axillary lymph node coverage with 3-dimensional tangential field irradiation and correlation with heart and lung dose.

PURPOSE: The American College of Surgeons Oncology Group Z0011 trial indicated no benefit from axillary lymph node (LN) dissection after a positive sentinel LN biopsy in patients receiving breast irradiation, suggesting that level I-II LNs were covered in tangential fields. METHODS AND MATERIALS: We evaluated 50 computed tomography-based tangential breast plans and contoured level I-III axillary LNs using the Radiation Therapy Oncology Group guidelines. The volumes of level I-III LN regions covered by 90% and 95% of the prescription dose (PD) were calculated and correlated with the V20 ipsilateral lung and mean heart dose. We calculated field length, distance from the humeral head, and separation. The Pearson correlation method and linear models were used in the correlative study. RESULTS: Level I LN mean and median volume (MMV) covered by 90% of the PD were 46.8% and 47.2%, respectively. MMV covered by 95% of the PD was 30.8% and 29.62%. Mean and median dose to level I LNs were 29.03 Gy and 30.13 Gy, respectively. The MMV of level II LNs covered by 90% of the PD was 2.49% and 0%. The mean and median dose to level II LNs were 6.09 Gy and 2.12 Gy, respectively. The MMV of level III LNs was 0% with a mean and median dose of 1.04 Gy and 0.92 Gy, respectively. There was a moderate correlation between the 95% prescription coverage of level I LNs and V20 ipsilateral lung and a smaller correlation between 95% prescription coverage of level I LNs and mean heart dose. Distance from the humeral head was inversely correlated with coverage of level I and II LNs and positively correlated with V20 lung. CONCLUSION: In most patients, <50% of the level I LN volume was covered by 90% of the PD and <30% was covered by 95%; <5% of the level II nodes were covered by 90% of the PD; and coverage was 0% for level III LNs.

Change in volume of lumpectomy cavity during external-beam irradiation of the intact breast.

PURPOSE: Definition of the lumpectomy cavity is an important component of irradiation of the breast. We use computed tomography (CT)-based planning and contour the lumpectomy volume on the planning CT. We obtained a second CT in the 4th or 5th week of treatment for boost planning and compared the volume change with the first planning-CT scan. METHODS AND MATERIALS: This retrospective study reviewed the planning-CT data for 20 patients. In the first CT, images were obtained from the mandible to 2 cm below the breast in 3-mm slices. In the second CT, for the boost, images were obtained from the top to the bottom of the clinically defined breast, in 3-mm slices. Lumpectomy cavities were contoured on both CT scans and volumes compared. RESULTS: Sixteen of the 20 patients (80%) had more than a 20% decrease from the first to the second volume, with a corresponding 95% confidence interval. The mean decrease was 16.13 cc, with a standard deviation of 14.05. The Spearman correlation coefficient of 0.18 did not show a significant correlation between the initial volume and the percent change. CONCLUSIONS: During external breast irradiation, many patients will have significant volume reduction in the lumpectomy cavity. Because CT-based definition of the lumpectomy cavity can influence the planning of a boost technique, further study appears warranted.