The treatment outcome of patients undergoing breast-conserving therapy: the clinical role of postoperative radiotherapy

BACKGROUND: Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. METHOD: There were 708 study subjects, all of whom had early breast cancer treated between 1992 and 2002. The median follow-up period was 83 months. After breast-conserving surgery, in patients with negative surgical margins, only tangential irradiation at 48 Gy/24 fr was performed. In contrast, in those with positive surgical margins, 10 Gy of radiation boost to the tumor bed with electrons was administered after tangential irradiation with 50 Gy/25 fr. Treatment outcome was analyzed using the Kaplan-Meier method and Cox's proportional hazards regression model. RESULTS: The disease-free survival and no-recurrence rates within the ipsilateral breast after 5 years were 93.4 and 97.2%, respectively. Risk factors for recurrence within the ipsilateral breast included younger age of patient, the number of positive lymph nodes, and no endocrine therapy. However, the surgical margin was not a risk factor. Risk factors for relapse outwith the ipsilateral breast included younger age, the number of positive lymph nodes, and recurrence within the ipsilateral breast. CONCLUSIONS: From our analysis of 708 Japanese women who received breast-conserving therapy, which can be regarded as a standard method in Japan, the treatment outcome was compatible with previous reports from other countries.     

Bilateral breast-conserving therapy for bilateral breast cancer: Results and consideration of radiation technique

BACKGROUND: Although breast-conserving surgery followed by definitive irradiation is an established treatment for patients with early breast cancer, the role of breast-conserving therapy (BCT) for patients with bilateral breast cancer has not been well studied and the radiation therapy technique is still under investigation. We examined the feasibility of breast-conserving therapy for bilateral breast cancer and present here our radiation therapy technique with CT simulator. METHODS: Between July 1990 and December 1998, we treated 17 patients with bilateral breast cancer who underwent bilateral breast-conserving surgery followed by definitive irradiation. Seven patients had synchronous bilateral breast cancer and ten had metachronous bilateral breast cancer. Radiation therapy consisted of 50 Gy to the bilateral whole breast in all patients but one. A CT simulator was used to plan a tangential radiation field to the breast in all patients. Boost irradiation of 10 Gy was administered to 8 tumors with close or positive margins. RESULTS: With a median follow-up periods of 95 months from each operation, no patients showed loco-regional recurrence on either side, and none suffered distant metastasis. Furthermore no serious late adverse effects were observed. CONCLUSION: This study demonstrated that BCT is feasible for bilateral breast cancer and the CT simulator is useful for determining the radiation field, especially when lesions are metachronous.     

Role of 10-Gy boost radiation after breast-conserving surgery for stage I–II breast cancer with a 5-mm negative margin

Background According to the Guidelines for breast-conserving therapy of the Japanese Breast Cancer Society, the surgical margin is “negative” when the minimum distance between the tumor edge and the margin of the resected specimen is more than 5 mm. The value of boost radiation for early breast cancer with a 5-mm negative margin remains unclear. Methods A total of 137 patients with stage I–II breast cancer underwent breast-conserving surgery between July 1987 and August 2002. All of the patients had negative margins according to the Japanese guidelines. Their median age was 50 years and the median follow-up period was 62 months. The entire ipsilateral breast was irradiated to a total dose of 50 Gy (25 fractions). Then an additional 10 Gy (5 fractions) was given to 79 patients, using 6- to 12-MeV electrons (boost group), while 58 patients (no-boost group) received no further radiation. Factors influencing local recurrence were evaluated by univariate and multivariate analyses. Results For the entire population, the 5-year overall survival, cause-specific survival, disease-free survival, and local recurrence rates were 96.0%, 96.8%, 94.2%, and 1.67%, respectively. Boost radiation reduced local recurrence, but the improvement was not significant (P = 0.070). Univariate and multivariate analyses failed to detect any factors that were significantly associated with local control. There were no severe complications in either group and there were no differences between the groups in the cosmetic outcome. Conclusion Boost radiation can be performed for stage I-II breast cancer with negative margins (Japanese guidelines), and showed a tendency to decrease local recurrence. A large randomized controlled study is necessary to establish final conclusions.     

A case of metachronous bilateral Breast Cancer with bilateral radiation pneumonitis after breast-conserving therapy

We report a patient with metachronous bilateral breast cancer who has twice developed radiation pneumonitis after breast-conserving therapy for each breast. The patient was a 48-year-old woman, who presented with Stage I right breast cancer. After wide excision of the right breast tumor and dissection of level I axillary lymph nodes, systemic therapy with oral 5-FU and tamoxifen was started. Subsequently, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Seven months after irradiation, she developed respiratory symptoms and radiation pneumonitis was diagnosed. The symptoms resolved with oral prednisolone. Thirty months after the right breast cancer treatment, Stage I left breast cancer was diagnosed. After wide excision of the left breast tumor and partial removal of the level I axillary lymph nodes, the same oral systemic chemo-hormonal therapy was initiated. Thereafter, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Four months after irradiation, she developed respiratory symptoms. A chest X-ray showed an area of increased density in the left lung consistent with radiation pneumonitis. The symptoms were mild and they improved spontaneously without medication. Although there is insufficient evidence to justify or withhold whole breast radiation therapy from patients with a history of contralateral breast cancer and radiation pneumonitis, it is essential to discuss the adequacy of whole breast irradiation and the possibility of alternative approaches, such as breast-conserving surgery without irradiation or partial breast irradiation for this rare condition.     

Results of Breast-Conserving Therapy for Ductal Carcinomain situ: The Kyoto University Experiences

BACKGROUND: The purpose of this study was to evaluate the results of breast-conserving therapy (BCT), defined as the combination of breast-conserving surgery with axillary dissection and definitive radiation therapy for ductal carcinoma in situ (DCIS). METHODS: Between November 1987 and March 1998, 33 patients with DCIS undergoing BCT at our hospital were examined. The mean age was 48. All patients underwent quadrantectomy or wide excision as well as axillary dissection. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was given to 15 patients with close or positive margins. Nearly all patients received adjuvant chemotherapy with 5-fluorouracil or its derivatives and adjuvant endocrine therapy with tamoxifen for 2 years. RESULTS: The minimum and median follow-up periods were 32 and 80 months, respectively. All patients but one were followed. Only one patient had a non-invasive local recurrence, 23 months after her operation. This patient was salvaged with simple mastectomy. Her prognostic index score was 8. The five-year local control rate was 97%. No serious acute or late complications were noted. CONCLUSION: The results of this retrospective study substantiate favorable data and appear to confirm the efficacy and reasonable local recurrence rate of BCT for the treatment of DCIS.     

Carcinomes canalaires in situ du sein traités par chirurgie conservatrice et irradiation avec complément dans le lit opératoire

PurposeWomen with ductal carcinoma in situ are treated with breast-conserving surgery and radiation therapy. The impact of an additive boost radiation is under evaluation.Patients and methodsAll women treated for ductal carcinoma in situ with breast-conserving surgery and whole breast radiation therapy at a total dose of 45 Gy with a boost radiation from 1990 to 2008 have been included in this retrospective monocentric retrospective study.ResultsWe included 171 patients. Boost radiation to the surgical bed was delivered by brachytherapy in 66 patients (39%), by direct en-face electron beam in 86 patients (50%), and by tangential fields using photon beams in 19 patients (11%). Median follow-up was 95.1 months. Eight local relapses (4.6%) have occurred. The 10-year local recurrence-free survival rate was 97%. The 10-year overall survival rate was 98%. On multivariable analysis, brachytherapy (P = 0.05; HR = 5.15; IC = 1–26.3) was associated with a reduction risk of local recurrence-free survival.ConclusionIn our experience, women treated for a ductal carcinoma in situ with breast-conserving surgery and whole breast radiation therapy with a boost radiation have a high 10-year local recurrence-free survival rate.     

Breast-conserving therapy after previous irradiation for lymphoma

There is an increased risk of breast cancer in patients who have undergone radiation treatment for lymphoma. While this usually precludes further radiotherapy (RT), we report five women who received irradiation for lymphoma and who subsequently received breast-conserving therapy between 1995 and 2007 for early-stage breast cancer. There was an overlap between the two treatment fields in all patients. RT for lymphoma ranged between 29.8 and 40 grays (Gy). The interval between lymphoma and the diagnosis of breast cancer was 11–24 years. All five patients had lumpectomy and received subsequent RT (45 Gy in four patients, 50 Gy in the other). All tolerated breast RT well, and toxicity was limited to grade 1 events. All five patients were alive at last follow-up, and there was no local recurrence in the irradiated breast in any patient. We conclude that previous RT for lymphoma is not necessarily an absolute contraindication to breast-conserving therapy.     

Current status of accelerated partial breast irradiation

Accelerated partial breast irradiation (APBI) is a radiotherapy method used in breast-conserving therapy. In APBI, the tumor bed is topically irradiated over a short period after breast-conserving surgery. The fundamental concept underlying APBI is that more than 70% of ipsilateral breast tumor recurrence occurs in the neighborhood of the original tumor, and that hypofractionated radiotherapy can be applied safely when the irradiated volume is small enough. It is expected to reduce the time and cost required for conventional whole breast irradiation while maintaining equivalent local control. Several techniques including multicatheter interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiation therapy, and 3D conformal external beam radiation therapy have been proposed, and each of them has its own advantages and drawbacks. Although APBI is increasingly used in the United States and Europe, and the short-term results are promising, its equivalence with whole breast radiation therapy is not fully established. In addition, because the average breast size in Japan is considerably smaller than in the West world, the application of APBI to Japanese patients is technically more challenging. At this point, APBI is still an investigational treatment in Japan, and the optimal method of radiation delivery as well as its long-term efficacy and safety should be clarified in clinical trials.     

Correlation of clinical and pathologic features with outcome in patients with ductal carcinoma in situ of the breast treated with breast-conserving surgery and radiotherapy

: Although breast-conserving surgery followed by radiotherapy (RT) has become a standard treatment option for patients with ductal carcinoma in situ of the breast, risk factors for ipsilateral breast tumor recurrence (IBTR) in these patients remain an active area of investigation. The purpose of this study was to evaluate the impact of clinical and pathologic features on long-term outcome in a cohort of DCIS patients treated with breast-conserving surgery plus RT.

: Between 1973 and 1998, 230 patients with DCIS were treated with breast-conserving surgery plus RT at our institution. All patients were treated by local excision followed by RT to the breast to a total median tumor bed dose of 64 Gy. Adjuvant hormonal therapy was used in only 20 patients (9%). All available clinical, pathologic, and outcome data, including ipsilateral and contralateral events, were entered into a computerized database. The clinical and pathologic variables evaluated included detection method, mammographic appearance, age, family history, histologic subtype, presence of necrosis, nuclear grade, final margin status, and use of adjuvant hormonal therapy.

: As of December 15, 2000, with a median follow-up of 8.2 years, 17 patients had developed a recurrence in the ipsilateral breast, resulting in a 5- and 10-year IBTR rate of 5% and 13%, respectively. Contralateral breast cancer developed in 8 patients, resulting in a 10-year contralateral recurrence rate of 5%. Patient age, family history, histologic subtype, margin status, and tumor grade were not significantly associated with recurrence on univariate analysis. A significantly higher rate of local relapse was observed in patients with the presence of necrosis. The 10-year relapse rate was 22% in 88 patients with necrosis compared with 7% in 142 patients without necrosis (p <0.01). In multivariate analysis, the presence of necrosis remained a significant predictor of local relapse. No breast relapses occurred among the 8 patients with positive margins, and three relapses developed among 21 patients with close margins. The rate of IBTR in those with close/positive margins did not differ from the rate in those with negative or unknown margins. It is also notable that none of the 20 patients treated with adjuvant tamoxifen had developed IBTR or a contralateral event to date, although the follow-up on this group was still too short to reach significance.

: In this cohort of uniformly treated patients with a relatively long follow-up, the presence of necrosis was a significant predictor of local relapse. However, positive or close margin status was not a significant predictor of local relapse. Although none of the patients receiving tamoxifen had a recurrence in the ipsilateral or contralateral breast, longer follow-up is required to assess the effect of tamoxifen on these end points.     

Factors Affecting Outcome for Young Women with Early Stage Invasive Breast Cancer Treated with Breast-conserving Therapy

Background Young women have worse outcome following breast-conserving therapy (BCT) than do older patients in many studies. We examined how clinical, pathological, and treatment factors affect these results. Methods Between 1993 and 1999, 130 patients age 40 years or younger with stage I or II breast cancer were treated with BCT. The median radiation dose to the tumor bed was 61 Gy; 80% of patients received chemotherapy; and 29% of 72 patients with estrogen-receptor positive tumors received tamoxifen. Median follow-up was 93 months. Results Fifteen patients (12%) developed an ipsilateral breast tumor recurrence (IBTR), with or without other simultaneous failure sites. The Kaplan-Meier 5- and 8-year actuarial rates were 8% and 14%, respectively. The 74 patients with grade 3 tumors had a higher IBTR rate (8-year actuarial rate, 18%) than the 54 patients with grade 1–2 lesions (7%) (P = 0.09). Six patients developed contralateral breast cancers, and 17 developed distant metastases (DM). The 8-year actuarial rates for freedom-from-DM, relapse-free survival, and overall survival were 85%, 72% and 96%, respectively. Conclusion This represents one of the largest series of young women treated with BCT, using an approach similar to current practice. The IBTR rate was substantially lower than in many past studies, but still higher than would be expected for older women. This appeared largely due to the increased rate of IBTR in patients with grade 3 tumors. If this observation is confirmed, further analysis of this subgroup may lead to ways of reducing the risk of IBTR.     

Clinical results of breast conserving therapy for stage I and II breast cancers: Assessment of local recurrences in relation to surgical margins

Background Because of previously reported shortened follow-up periods, breast conserving therapy is still not prevalent for patients with breast cancer in Japan. This is a report of clinical trial results. Methods Between November 1987 and October 1995, breast carcinomas in 462 patients were treated with breast conserving therapy (BCT). Three hundred and sixty-four patients with follow-up periods of longer than 1 year, excluding simultaneous bilateral breast carcinomas, were analyzed. There were 19 stage 0,211 stage I, 132 stage II, and 2 stage III tumors according to the 1987 UICC classification. A total dose of 50 Gy was delivered over 5 weeks to the preserved breast using⁶⁰Co γrays. The primary site was boosted with a total dose of 10 Gy in 5 fractions in 40 of the 83 patients whose tumor margins were either positive or close. Results In a follow-up period of 12 to 96 months with a median of 35 months, 8 patients developed a breast recurrence. The actuarial overall, relapse-free, and breast-recurrence-free survival at 5 years were 99.0%, 92.3%, and 97.8%, respectively. The difference in the local control rate was significant between patients with negative margins and those with positive margins (P<0.0001), and between the patients with negative margins and those with close margins (P=0.0284). Conclusions The 5-year results of our trial were similar to those of other reported series. Positive and close margins are risk factors for breast recurrence. Improvements in optimal methods of radiation therapy including boost irradiation are needed.     

Whole-breast radiotherapy with shorter fractionation schedules following breast-conserving surgery: short-term morbidity and preliminary outcomes

Background The success of whole-breast radiotherapy with shorter fractionation schedules following BCS has rarely been evaluated in Japanese women. Here we present the short-term morbidity and preliminary outcomes of the shorter fractionation regimen initiated at the Kawasaki Medical School Hospital in 2003. Methods Between January 2003 and December 2005, 248 patients (251 breasts) with breast cancer underwent short-course RT following BCS. The whole breast was irradiated with a total dose of 42.5–47.8 Gy in 16–20 fractions. Patients with positive margins received additional boost irradiation to the tumor bed of 10–13.3 Gy in 4–5 fractions using 4–11 MeV electrons. Adjuvant therapy was administered in 217 cases. Results The median follow-up time was 26 months. The actuarial 4 year overall, cause specific, and disease-free survival rates were 96.7, 98.6, and 94.9%, respectively. Local recurrence was observed in one patient and distant metastases in four. The 4 year local control rate was 99.0%. A total of 221 patients developed radiation dermatitis (207 patients with grade 1, 14 patients with grade 2). The incidence of grade 2 dermatitis correlated with patient age. Radiation pneumonitis was observed in 15 patients (nine patients with grade 1, six with grade 2), two of whom developed BOOP. No difference was found in age, irradiated breast site, or use of boost irradiation, chemotherapy, and tamoxifen between those with and without pneumonitis. Conclusions The short fractionation regimen results in acceptable short-term morbidity. With limited follow-up, the incidence of recurrence in the treated breast was low.     

Impact of Regional Nodal Irradiation and Hypofractionated Whole-Breast Radiation on Long-Term Breast Retraction and Poor Cosmetic Outcome in Breast Cancer Survivors

PurposeWe performed a prospective longitudinal study to determine predictors of long-term breast asymmetry in breast cancer patients treated with breast-conserving surgery and whole-breast external-beam radiotherapy (XRT).Patients and MethodsA total of 109 patients with stage 0 to III breast cancer treated with breast-conserving surgery followed by conventional (50 Gy plus boost) or hypofractionated (39.9 Gy with simultaneous integrated boost of 48 Gy) XRT were enrolled onto 2 studies of XRT-induced skin toxicity before (baseline), during, and 1 year after XRT. Using baseline and 1-year post-XRT photographs, breast asymmetry was objectively quantified by calculating the percentage breast retraction assessment (pBRA), with larger values indicating more asymmetry. Skin thickness ratio (STRA) values were calculated using ultrasound images. Univariate and multivariate analyses were conducted to determine the relationship among STRA-, patient-, tumor-, and treatment-related factors, and pBRA.ResultsSeventy-one patients (65%) had more breast asymmetry (positive change in pBRA) 1 year after XRT relative to baseline. Only pre-XRT STRA was associated with a higher pre-XRT baseline pBRA in multivariate analysis (P = .02). Larger breast volume, baseline pBRA, conventionally fractionated (vs. hypofractionated) XRT, supraclavicular nodal irradiation, and higher STRA at 1 year predicted for higher long-term pBRA in the multivariate model (all P < .05). Breast volume and supraclavicular nodal irradiation were associated with the largest changes in breast asymmetry (all P < .05).ConclusionThis prospective longitudinal study confirmed the known impact of breast volume, surgery, and XRT on breast asymmetry. We also found that supraclavicular nodal irradiation and conventionally fractionated XRT are associated with worse cosmetic outcome 1 year after XRT.     

Preliminary Results of a Randomized Study on Postmenopausal Women With Early Stage Breast Cancer: Adjuvant Hypofractionated Whole Breast Irradiation Versus Accelerated Partial Breast Irradiation (HYPAB Trial)

BackgroundThe purpose of this study was to report preliminary data of a randomized phase III trial comparing hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) using volumetric modulated arc therapy (VMAT).Material and MethodsThe HYPAB trial enrolled postmenopausal women with biopsy-proven infiltrating breast cancer, clinically negative axilla, single T1 to T2 tumors, who were treated with breast-conserving surgery. Patients were randomized 1:1 after surgery to HWBI (40.5 Gy whole breast, 48.0 Gy to surgical bed, 15 fractions over 3 weeks) or APBI (30 Gy delivered in 5 fractions of 6 Gy given on alternate days on the surgical bed). Cosmetic outcome was the primary end point of the study.ResultsA total of 172 patients were enrolled. After a median follow-up of 36 months, 5 local failures and 3 locoregional failures were recorded, with no difference between the 2 treatment arms. Use of HWBI as compared with APBI was significantly correlated with increased incidence of overall (62% vs. 14%; P < .001) and grade 2 (18% vs. 1%; P < .001) acute skin toxicity. APBI was correlated with a lower incidence of overall late toxicity as compared with HWBI (18% vs. 41%; P = .001), but no significant difference was found in term of occurrence of grade 2 events (1% vs. 4%; P = NS). At comparative assessment between baseline and post-radiotherapy evaluation, impairment in cosmetic outcome was reported in 19 (11%) patients. Owing to premature closure of the study, no per-protocol comparison between the treatment arms was performed.ConclusionAPBI with the VMAT technique is safe and feasible, with lower acute toxicity when compared with HWBI.     

Intensity-modulated tangential beam irradiation of the intact breast

Purpose: To evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast.

Methods and Materials: Three-dimensional treatment planning was performed on five left and five right breasts using standard wedged and intensity modulated (IM) tangential beams. Optimal beam parameters were chosen using beams-eye-view display. For the standard plans, the optimal wedge angles were chosen based on dose distributions in the central plane calculated without inhomogeneity corrections, according to our standard protocol. Intensity-modulated plans were generated using an inverse planning algorithm and a standard set of target and critical structure optimization criteria. Plans were compared using multiple dose distributions and dose volume histograms for the planning target volume (PTV), ipsilateral lung, coronary arteries, and contralateral breast.

Results: Significant improvements in the doses to critical structures were achieved using intensity modulation. Compared with a standard-wedged plan prescribed to 46 Gy, the dose from the IM plan encompassing 20% of the coronary artery region decreased by 25% (from 36 to 27 Gy) for patients treated to the left breast; the mean dose to the contralateral breast decreased by 42% (from 1.2 to 0.7 Gy); the ipsilateral lung volume receiving more than 46 Gy decreased by 30% (from 10% to 7%); the volume of surrounding soft tissue receiving more than 46 Gy decreased by 31% (from 48% to 33%). Dose homogeneity within the target volume improved greatest in the superior and inferior regions of the breast (approximately 8%), although some decrease in the medial and lateral high-dose regions (approximately 4%) was also observed.

Conclusion: Intensity modulation with a standard tangential beam arrangement significantly reduces the dose to the coronary arteries, ipsilateral lung, contralateral breast, and surrounding soft tissues. Improvements in dose homogeneity throughout the target volume can also be achieved, particularly in the superior and inferior regions of the breast. It remains to be seen whether the dosimetric improvements achievable with IMRT will lead to significant clinical outcome improvements.     

Preliminary results of quadrantectomy and radiation therapy for breast cancer

Between November 1987 and December 1992, a total of 200 breast carcinomas in 199 patients were treated by definitive radiation therapy following quadrantectomy and level III axillary dissection. One patient with simultaneous bilateral breast cancers was excluded and 198 patients with breast cancer were enrolled in this study. There were 9 Stage 0, 117 Stage I and 72 Stage II tumors by the UICC tumor classification system (1987). Histological examination revealed that 9 tumors were non-invasive carcinomas and 189 were invasive carcinomas. For radiation therapy, a total of 50 Gy was delivered to the ipsilateral breast using⁶⁰Co γ rays. In three cases with level III lymph node involvement, the ipsilateral supraclavicular and parasternal regions were also irradiated. Boost irradiation was given to 8 of 12 margin-positive patients, and 2 of 24 patients in whom tumor cells were present within 5 mm from the margin. We used a CT simulator for the treatment planning of radiation therapy in 196 tumors. During follow-up for 16-77 months (median: 35 months), 2 patients died of unrelated causes and 6 developed distant metastasis (4 to bone and 2 to lung). Local recurrence was noted in 1 patient. Acute reactions to radiation therapy included moist desquamation involving the tip of the breast and the axilla in 14 and 5 patients, respectively, as well as bright erythema in 7 patients. Late reactions included arm edema in 12 patients, patchy depigmentation at the tip of the breast in 5 patients, moderate telangiectasia in 1 patient, and symptomatic radiation pneumonitis in 1 patient. The actuarial overall survival, cause-specific survival, disease-free survival, and relapse-free survival rates at 5 years were97.2%, 100%, 93.5%, and 93.0%, respectively. This excellent locoregional control, together with a highly acceptable toxicity strongly suggests the usefulness of quadrantectomy and radiation therapy for Japanese women with breast cancer. The possible indications include clinical Stage 0 and, I breast cancer, and clinical Stage II cancer in patients with relatively large breasts and with the primary tumor not located close to the nipple.     

Avascular necrosis of bilateral femoral head as a result of long-term steroid administration for radiation pneumonitis after tangential irradiation of the breast

We report a patient with avascular necrosis of the bilateral femoral head resulting from long-term steroid administration for radiation pneumonitis that occurred after tangential irradiation of the breast. The patient was a 50-year-old postmenopausal woman with breast cancer, stage IIIB (T4bN0M0) in the right C area. Following wide excision of right breast carcinoma and level III axillary lymph node dissection, whole-breast X-ray irradiation was given, at a dose of 2 Gy per fraction; the total dose was 50 Gy. On day 84 after the initiation of radiation therapy, she developed radiation pneumonitis. As the lung shadow expanded to the contralateral lung, she received steroid medication. Despite the steroid medication, the symptoms were exacerbated; therefore, she underwent steroid pulse administration with subsequent oral steroid medication. She improved immediately, but subsequently the radiation pneumonitis relapsed three times when the steroid medication was stopped. The period of medication was 423 days and the cumulative amount of steroids was 7365 mg before complete resolution occurred. In the 19 months after she stopped the steroid administration, she developed avascular necrosis (AVN) of the bilateral femoral head. This was regarded as a complication of the steroid treatment. Patients treated with long-term or high-dose steroid administration have been suggested to be at great risk of developing AVN, but this hypothesis remains controversial. The probability of AVN occurrence may be very small, but it should be considered as one of the complications of steroids, which are often used to treat radiation pneumonitis.     

Outcome of breast-conserving therapy in the Tokyo women’s medical university breast cancer society experience

BACKGROUND: The results of BCT in Japanese women have not been fully evaluated. The Tokyo Women's Medical University Breast Cancer Society initiated BCT protocols in 1987. Here, we present a retrospective analysis of BCT outcomes and identify prognostic factors. METHODS: The study population comprised 348 patients (353 breasts) with UICC clinical stage 0,I or II breast cancer, for whom wide excision (n= 294), quadrantectomy (n= 56) and tumorectomy (n= 3) were performed. The final pathological margin states were positive in 102 breasts (cancer cells remained within 5 mm of the surgical margin). The whole breast was irradiated to a total dose with 44 Gy/20 fractions or 46 Gy/23 fractions in the patients with negative surgical margins. The patients with positive or close margins received 48.4 Gy/22 fractions or 50 Gy/25 fractions irradiation to the whole breast. All but 2 patients received a radiation boost to the tumor bed and all tumor beds were irradiated to more than 53 Gy. Adjuvant therapy was administered in 240 cases. The median follow-up time was 4.3 years. RESULTS: The 5-year overall, cause-specific and disease-free survival rates were 95.8%, 97.3% and 92.5%, respectively. Recurrence was observed in 29 patients including 11 patients with loco-regional recurrence. Local recurrence was observed in 6 patients, 5 of whom were premenopausal. The 5-year local control and loco-regional control rates were 98.9% and 96.6%, respectively. T status (T1 to T2) was the only significant prognostic factor for disease-free survival. No severe morbidity has been observed. Cosmetic results were excellent or good in 73% of patients. CONCLUSION: Our BCT protocols provide a high rate of local control and good cosmetic outcome. Pathologic margin status was not a major prognostic factor for local recurrence. Long term follow-up is required to reach a definite conclusion on optimal BCT protocols.     

Treatment outcome of breast-conserving therapy in patients with positive or close resection margins: Japanese multi institute survey for radiation dose effect

BACKGROUND: The relationship between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) is controversial. To evaluate the radiation dose and other factors influencing the ipsilateral breast tumor control (IBTC) in patients with positive or close resection margins after breast conserving surgery (BCS), the Japanese Radiation Oncology Study Group (JROSG) S-99-3 study group conducted a multi-institute survey of these patients. METHODS: The patients with less than 5 mm tumor-free margins after BCS were eligible for this study. A total of 971 patients from 18 institutes were enrolled in the analysis. The final pathological margin status was classified into 3 groups. Radiation doses to the tumor bed were less than 60 Gy in 252 patients, 60 Gy in 456 patients and more than 60 Gy in 233 patients. RESULTS: IBTR was observed in 55 patients (5.8%). The IBTC rates at 5 and 10 years by the Kaplan Meier method were 95.6% and 87.3%, respectively. There was no significant difference in 10-year IBTC rates according to marginal status; 85.9% in positive margin patients, 91.0% in equal or less than 2 mm margin patients and 87.0% in 2.1-5 mm margin patients. Radiation dose to the tumor bed was a marginally significantly associated with the 10-year IBTC rate (> or = 60 Gy 90.8% vs < 60 Gy 84.2%, p = 0.057). In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better (p = 0.039). The other factors influencing the IBTC were age (> or = 35 years vs < 35 years: p < 0.0001), menopausal status (p < 0.0001) and tumor size (p = 0.023). CONCLUSIONS: In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better than the others. We recommend that the tumor bed be irradiated with at least 60 Gy in the patients with positive margins. Further follow-up is necessary to draw final conclusions.     

Intraoperative radiation therapy delivered prior to lumpectomy for early-stage breast cancer: a single institution study

Objective: To evaluate the safety, cosmesis, and clinical outcome of intraoperative electron radiation therapy (IOERT) delivered prior to lumpectomy for early-stage breast cancer. Methods: From December 2008 to March 2012, 75 breast cancer patients (ages 34-66 years) were treated with IOERT during breast conservative surgery. IOERT was delivered using a mobile linear accelerator. Suitable energy and applicator size were chosen to ensure coverage of the tumor with anterior and posterior margins of 1 cm and lateral margins of 2 cm. Patients with sentinel node metastases or younger than 40 years received 8 Gy as boost followed by post-operative external beam radiation therapy of 50 Gy/25F; the others had 15 Gy, prescribed to the 90% isodose depth. Adjuvant treatment consisted of chemotherapy (55 patients), hormonal therapy (59 patients), or combined chemotherapy and hormonal therapy (41 patients). The safety, cosmesis, and short-term outcome were evaluated. Results: Median follow-up was 54 months (range: 30-66 months). Two (2.7%) patients developed post-surgical hematoma. Six (8.0%) patients developed mild breast fibrosis. Eight (10.7%) patients suffered from local pain. One (1.2%) patient experienced a post-operative infection. Sixteen (21.3%) patients developed Grade 1 pulmonary fibrosis. Forty-three (57.3%) patients had an excellent cosmetic result and 23 (30.7%) had a good cosmetic result. Three patients had an ipsilateral breast recurrence, with an actual 3-year local recurrence rate of 4.0%. One patient had an ipsilateral axillary recurrence, resulting in a 3-year regional recurrence rate of 1.3%. No distant metastases or deaths were observed. The 3-year disease free survival was 94.6%. Conclusions: Intraoperative electron radiation therapy delivered prior to lumpectomy is safe and feasible for selected patients with early-stage breast cancer. Early side effects, cosmesis and short-term efficacy are acceptable, but a longer follow-up is needed for evaluation of late side effects and long-term outcome.