Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions

PurposeTo assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction).Methods and materialsPatients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1–T2 pN0–N1a) invasive ductal carcinoma.Results77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged “good/excellent” and “poor” in 75 (97%) and in 2 (3%) patients, respectively.Conclusions40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.     

Once‐weekly hypofractionated radiotherapy for breast cancer: First results of a phase II clinical trial

Hypofractionated radiotherapy (HF) in 15 or 16 daily fractions is well established as an alternative in early breast cancer after breast‐conserving surgery. Evidences for a whole‐breast treatment even shorter, in 5‐10 fractions, are still scarce. Women 50 years or older, with early breast tumor (pT1‐2pN0), after breast‐conserving surgery were eligible to enter in this phase II trial and received whole breast once‐weekly hypofractionated radiotherapy (wHF‐RT) to a total dose of 30 Gy, in 5 fractions of 6 Gy. During treatment and in post‐treatment follow‐up the toxicity was assessed and graduated according to the “Common Terminology Criteria for Adverse Events” (CTCAE), v3.0. Breast pictures for esthetic comparison were taken in 5 timepoints and 2 breast surgeons independently graduated the cosmetics changes. The trial was registered with ClinicalTrials.gov, number NCT01965483. From October 2013 to November 2015, 44 patients were enrolled in the trial and treated according to the protocol of wHF‐RT. The median age was 70.5 years (51‐88 years), and the median follow‐up was 22 months (9‐33 months). Skin erythema was the most common acute adverse event. At the end of radiation, 30 patients (68.2%) had any grade of radiation dermatitis. Concerning cosmetic appearance, there was no significant difference between pretreatment and 1 year assessments. The 2‐year overall survival and disease‐free survival were, respectively 96.8% and 97.7%. There was only one distant recurrence and no local or regional recurrence. Once‐weekly hypofractionated radiotherapy is a feasible and well tolerated alternative for early breast cancer adjuvant management with acceptable acute toxicity and esthetic outcomes.     

Accelerated hypofractionated adjuvant whole breast radiotherapy with concomitant photon boost after conserving surgery for early stage breast cancer: a prospective evaluation on 463 patients

The current standard therapeutic option for early stage breast cancer (EBC) employs a multimodality treatment approach including conservative surgery, radiotherapy, chemotherapy, and hormone therapy. The most common adjuvant radiotherapeutic strategy consists of external beam radiation therapy (EBRT) delivered to the whole breast using 1.8-2 Gy fractions given five times a week, up to a total dose of 45-50 Gy over a period of 5 weeks. In recent years, altered schedules employing larger dose per fraction delivered in fewer treatment sessions over a shorter overall treatment time began to be explored. We herein present clinical data on accelerated hypofractionated adjuvant whole-breast radiotherapy delivered on a daily basis for a total treatment time of 20 fractions. Between February 2005 and June 2009, a total of 463 patients underwent hypofractionated accelerated adjuvant radiation after conservative surgery for early breast cancer (pathological stage pTis, pT1 or pT2, pN0-N1). The basic course of radiotherapy consisted of 45 Gy, to the whole breast in 20 fractions with 2.25 Gy/fraction; an additional daily boost dose of 0.25 Gy was concomitantly delivered, to the lumpectomy cavity, for an additional total dose of 5 Gy. The cumulative nominal dose was 50 Gy. At follow-up, patients were examined at 3 and 6 months after the end of radiotherapy and twice a year afterward. Toxicity was scored according to the Common Terminology Criteria for Adverse Events, using the Radiation Therapy Oncology Group /European Organization for Research and Treatment of Cancer toxicity scale. Cosmetic results were assessed in agreement with the Harvard criteria. All the 463 patients treated with the accelerated hypofractionated adjuvant whole-breast radiotherapy schedule achieved at least 6 months' follow-up and subsequently were considered for the present analysis. With a median follow-up of 27 months, 5-year DFS is 93.1%. Only three patients experienced disease recurrence: two of them with an axillary nodal relapse; one patient with systemic spread. No local relapse occurred. No major toxicities (grade 3 or more) were detected during follow-up. Only 2% of the patients experienced grade 3 skin toxicity at the very end of the radiotherapy course. Cosmetic result was assessed and scored at 6 months, 1 year, 2 years: 100% of patients showed excellent or good cosmetic result. The explored accelerated hypofractionated adjuvant radiotherapeutic approach for early breast cancer with concomitant photon boost seems to be feasible providing consistent clinical results with excellent short-to-medium-term toxicity profile.     

Relation between Hypofractionated Radiotherapy,Toxicity and Outcome in Early Breast Cancer

To compare adjuvant conventional radiotherapy (C‐RT) to hypofractionated schedule (HF‐RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C‐RT (50 Gy; 2 Gy/fr) or HF‐RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT‐induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation‐related toxicity. No increase in late toxic effects has been reported between C‐RT and HF‐RT schedules. Overall, the 2‐year disease free survival was 94.4%. HF‐RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control.     

A retrospective analysis on safety and effectiveness of hypofractioned post‐mastectomy radiotherapy

The data supporting hypofractionated post‐mastectomy radiotherapy is limited. The purpose of this study is to present the experience from Tarnów of hypofractionated PMRT over 20 fractions with respect to toxicity and effectiveness. We delivered post‐mastectomy radiotherapy at the dose of 45 Gy in 20 fractions to the chest wall and the draining regional lymph nodes. The primary outcome of interest was to ensure that the rate of grade 3 or greater toxicity from the hypofractionation, at any time point, was non‐inferior to standard post‐mastectomy radiotherapy. We conducted a retrospective analysis of 211 women with stages I‐IV breast cancer. After a median follow‐up of 30 months, there were four reported grade 3 toxicities, with grade 3 lymphedema being the most frequent (1.5%). There were 134 reported grade 2 toxicities, with grade 2 fatigue being the most frequent (18%). There were six instances of isolated locoregional (6 of 211; 2.8%). Three‐year estimated local recurrence‐free survival was 96.4% (95% CI 0.921‐0.984). The 3‐year estimated distant recurrence‐free survival was 77.8% (95% CI 0.699‐0.838). To our knowledge, the results presented here are the largest single institution experience of hypofractionated post‐mastectomy radiotherapy published in the literature to date. Our fractionation scheme, 45 Gy in 20 fractions, seems to be safe and effective with low toxicity.     

Postoperative intensity-modulated radiotherapy with simultaneous integrated boost in prostate cancer: A dose-escalation trial

ObjectivesTo determine the recommended phase II dose of postoperative accelerated intensity modulated radiotherapy (IMRT) for prostate cancer.Material and methodsStep and shoot IMRT with simultaneous integrated boost (SIB) was delivered in 25 fractions over 5 weeks to patients with high risk resected prostate adenocarcinoma (stage pT3-4 and/or positive surgical margins). Pelvic nodes received 45 Gy at 1.8 Gy/fraction; dose escalation was performed only to the prostate bed (planned dose escalation: 56.8 Gy at 2.27 Gy/fraction, 59.7 Gy at 2.39 Gy/fraction, 61.25 Gy at 2.45 Gy/fraction, 62.5 Gy at 2.5 Gy/fraction). Dose-limiting toxicity (DLT) was any grade ≥ 3 acute toxicity (RTOG score).ResultsTwenty-five patients were treated: 7 patients at the 56.75 Gy dose level, 6 patients at each subsequent dose level. Pathologic stages were: pT2c: 2; pT3a: 11; pT3b: 12; pN0: 22; pN1: 3; R0: 7; R1: 18. Median follow-up time was 19 months (range: 6–36 months). No patient experienced DLT. Grade 1–2 acute rectal and urologic toxicity was common (17 and 22 patients, respectively).ConclusionsThe recommended dose was 62.5 Gy in 2.5 Gy/fraction. Postoperative hypofractionated IMRT SIB for prostate cancer seemed to be well tolerated and could be tested in phase II studies.     

The Impact of Intermediate Time between Chemotherapy and Hypofractionated Radiotherapy to the Radiation Induced Skin Toxicity for Breast Adjuvant Treatment

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty‐four patients with stage I–II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose‐EQD2‐ 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow‐up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late‐toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.     

Accelerated partial breast irradiation using 3D conformal radiotherapy: Toxicity and cosmetic outcome

PurposeThe aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI).Methods and materials84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose–volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale.ResultsMedian patient age was 66 years (range 51–87). Median follow-up was 36.5 months (range 13–83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45).ConclusionsAPBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse.     

Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy

PurposeTo evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity.Methods and materials537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis.ResultsThe mean age was 74 (range 46–91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months.G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively.Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis.ConclusionsThe results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity.     

Initial outcomes with image‐guided partial breast irradiation delivered with intensity‐modulated radiation therapy

Patients were treated at a single institution to a dose of 30 Gy in five fractions delivered every other day using image‐guided intensity modulated radiation therapy (IMRT) partial breast irradiation. A total of 34 patients were treated with a median follow‐up of 4.6 months. The rate of acute Grade 1 dermatitis was 23.5% (n = 8), and Grade 1 fatigue was 17.6% (n = 6), with no Grade 2 or higher acute toxicities. The rate of chronic Grade 1 dermatitis was 25.0% (n = 6), Grade 1 fat necrosis 4.2% (n=1), with no patients demonstrating other chronic toxicities. Image‐guided APBI delivered with IMRT is associated with low rates of acute and chronic toxicity though additional follow‐up is warranted.     

Six‐year Outcome of a Prospective Study Evaluating Tumor Bed Boost with Intra‐operative Electron Irradiation Followed by whole‐Breast Irradiation for Early‐Stage Breast Cancer

A prospective study was performed for patients with early‐stage breast cancer in which a single fraction of intraoperative electron irradiation (IOERT) was given to the tumor bed, followed by conventional fractionated whole‐breast irradiation (WBRT). Patients with T1/T2N0 breast cancer underwent lumpectomy and sentinel lymph node biopsy. A tumor bed boost of 10 Gy of IOERT using 6–12 MeV electrons was administered by a dedicated mobile linear accelerator in the operating room. After adequate wound healing, 48 Gy WBRT was given to the whole breast in 24 fractions. Fifty‐two patients were enrolled between February 2003 and January 2005. At a median follow‐up of 79 months, there were two local relapses. The 6‐year actuarial overall survival and distant control rates were 89% and 96%, respectively. At last follow‐up, cosmesis was graded as excellent or good in 45 (87%), fair in five (10%), and poor in two patients (4%), respectively. Difficulty in wound healing occurred in two patients who had additional surgery later. One patient developed significant fibrosis after aspiration of a symptomatic seroma. The result of this pilot study shows the feasibility of using IOERT as the tumor bed boost in lieu of 6–8 days of standard electron beam treatment with good local control and cosmetic results. However, late surgical intervention of the lumpectomy bed may result in more pronounced tissue fibrosis and wound healing difficulty.     

Hypofractionated Radiation Therapy for Early Stage Breast Cancer: Outcomes,Toxicities, and Cost Analysis

A French prospective randomized trial comparing whole breast radiotherapy with 45 Gy in 25 fractions versus 23 Gy in four fractions demonstrated equivalent 5‐year local control and survival. On the basis of this data, we offer the hypofractionated regimen to women who refuse to undergo standard radiotherapy. We report our outcomes and a cost analysis. Between 2000 and 2012, 84 patients participated in this IRB‐approved study and underwent whole breast radiation to 23 Gy in four fractions. Local control and survival were analyzed using the Kaplan–Meier method. Acute toxicities and overall long‐term cosmetic results were assessed. Costs were estimated from 2012 Medicare reimbursement data and compared to costs from standard courses of 25 and 16 fractions. All 84 patients are included in this report. Median age was 83 (range 42–98). Most patients had stage I (80%), hormone receptor positive (90%) breast cancer. Fifty‐eight patients (69%) were treated prone and 26 (31%) supine. At a median follow‐up of 3 years, one local recurrence has occurred, of ductal carcinoma in situ histology. Among the 13 patients deceased, two died of metastatic breast cancer. Five‐year actuarial local control is 99%, breast cancer‐specific survival is 98%, and overall survival is 79%. Toxicities were limited to grade 1 dermatitis in 32 patients (38%) and grade 2 fatigue in three (4%). Sixty‐three patients (75%) reported good or excellent cosmetic outcome at their last follow‐up. Collected Medicare reimbursement was $4,798 for the hypofractionated course. Compared to the projected reimbursement of standard regimens, $10,372 for 25 fractions and $8,382 for 16 fractions, it resulted in a difference of $5,574 and $3,584, respectively. At a follow‐up of 3 years, this hypofractionated regimen appears to be a promising approach, primarily for elderly women who are unable to undergo longer treatment courses but have indications for whole breast radiotherapy.     

Acute toxicity and health-related quality of life after accelerated whole breast irradiation in 5 fractions with simultaneous integrated boost

IntroductionAcceleration of radiotherapy in 5 fractions for breast cancer can reduce the burden of treatment. We report on acute toxicity after whole-breast irradiation with a simultaneous integrated boost in 5 fractions over 10–12 days.Material and methodsAcute toxicity and health-related quality of life (HRQoL) of 200 patients, randomized between a 15- or 5-fractions schedule, were collected, using the CTCAE toxicity scoring system, the Multidimensional Fatigue Inventory, EORTC QLQ-C30 and BR23 and the BREAST-Q questionnaire. The prescribed dose to the breast was either 1512.67 Gy (40.05 Gy) or 515.7 Gy (28.5 Gy). 90% of patients received a SIB to a cumulative dose of 46.8 Gy (1513.12 Gy) or 31 Gy (516.2 Gy).ResultsPhysician-assessed toxicity was lower for the 5-fractions group. A significant difference was observed for breast pain (p = 0.002), fatigue (p < 0.0001), breast edema (p = 0.001) and dermatitis (p = 0.003). Patients treated in 5 fractions reported better mean HRQoL scores for breast symptoms (p = 0.001) and physical well-being (p = 0.001). A clinically important deterioration in HRQoL of 10 points or more was also less frequently observed in the latter group for physical functioning (p = 0.0005), social functioning (p = 0.0007), fatigue (p = 0.003), breast symptoms (p = 0.0002) and physical well-being (p = 0.002).ConclusionIn this single institute study, acute toxicity of accelerated breast radiotherapy in 5 fractions over 10–12 days seems to compare favourably to hypofractionated breast radiotherapy in 15 fractions. Less breast edema, dermatitis, desquamation, breast pain and fatigue are seen. Social and physical functioning are also less disturbed and patients have a better future perspective.     

Single Institution trial of anthracycline‐ and taxane‐based chemotherapy for operable breast cancer: The ASTER study

The efficacy of anthracycline‐ and taxane‐based chemotherapy for perioperative treatment of breast cancer (BC) has been established. No superiority of a cytotoxic regimen has been demonstrated, provided that administration of an anthracycline and a taxane is warranted. The ASTER study was designed to investigate the safety of 6 months of perioperative chemotherapy with Doxorubicin and Paclitaxel, followed by Cyclophosphamide, Methotrexate, and 5‐Fluorouracil. ASTER enrolled patients with cT2‐3 N0‐1 or pT1‐2 N1‐3 BC, from November 2008 to August 2011. Treatment consisted of Doxorubicin 60 mg/sm, Paclitaxel 200 mg/sm q21 (AT) for three cycles followed by Cyclophosphamide 600 mg/sm, Methotrexate 40 mg/sm, 5‐Fluorouracil 600 mg/sm d1,8 q28 (CMF) for three cycles, in either neo‐adjuvant or adjuvant setting. All HER‐positive patients received targeted therapy with Trastuzumab for 1 year. Disease‐free and overall survival (DFS and OS, respectively) were estimated according to Kaplan‐Meier method. Three hundred and thirty patients were enrolled, where 77.9% of cases were treated in an adjuvant setting; 65.5% received breast conservative surgery, 72.4% axillary dissection. 75.5% of cases presented estrogen receptor positivity, 66.7% progesterone receptor positivity; 18.5% of patients presented HER2‐positive BC, 16.1% triple negative disease. Twenty‐eight (8.5%) developed grade III‐IV hematologic toxicity; nine patients (2.7%) developed grade III neurological toxicity. Loco‐regional DFS was 99.6% at 1 year, 97.1% at 5 years, 95.9% at 7 years. Corresponding distant DFS was 98.4%, 90.2%, and 88.8%. One, 5, and 7‐year OS was 99.6%, 94.9%, and 91.2%, respectively. Chemotherapy with ATx3→CMFx3 is confirmed safe and effective at 6.7 years follow‐up. These results appear comparable to those reported in regulatory trials of most commonly prescribed anthracycline and taxane‐based regimens.     

Biliary tract cancer treatment: 5,584 results from the Biliary Tract Cancer Statistics Registry from 1998 to 2004 in Japan

Background/Purpose  The results from the Japanese Biliary Tract Cancer Statistics Registry from 1988 to 1998 were reported in 2002. In the present study, we report here selectively summarized data as an overview of the 2006 follow-up survey of the registered cases from 1998 to 2004 for information bearing on problems with the treatment of cancer of the biliary tract. Methods  A total of 5,584 patients were registered from 1998 to 2004. The site of cancer was the bile duct in 2,732 patients, the gallbladder in 2,067, and the papilla of Vater in 785. Those cases were analyzed with regard to patient survival according to the extent of tumor invasion (pT), the extent of lymph node metastasis (pN) and the stage. Results  The five-year survival rate after surgical resection was 33.1% for bile duct cancer, 41.6% for gallbladder cancer, and 52.8% for cancer of the papilla of Vater. For hilar or superior bile duct cancer, the 5-year survival rate was lower with an increase in the pT, pN and f stage, except pT3 vs. pT4, pN1 vs. pN2 and stage III vs. stage IVa. For middle or distal bile duct cancer, the 5-year survival rate was lower with increase in pT, pN and f stage, except pT2 vs. pT3, pN2 vs. pN3, stage II vs. stage III and stage III vs. stage IVa. For gallbladder cancer, the 5-year survival rate was lower with increase in pT, pN and f stage. For cancer of the papilla of Vater, the 5-year survival rate was lower with increase in pT, pN and f stage, except pT1 vs. pT2, pN1 vs. pN2, and stage III vs. stage IVa. Conclusions  In the present study, the outcomes of surgical treatment were better than that of the previous report from Japan and foreign countries. The pT, pN and stage of gallbladder cancer are well defined. However, there were no significant differences in some groups of those of bile duct cancer and cancer of the papilla of Vater.     

Hypofractionation with simultaneous integrated boost after breast-conserving surgery: Long term results of two phase-II trials

PurposeTo analyze long-term results of two multicenter prospective single-arm trials (ARO-2010-01 and ARO-2013-04) investigating adjuvant hypofractionated radiotherapy (HF) with simultaneous integrated boost (SIB) after breast-conserving surgery (BCS).MethodsEligible patients had histopathologically confirmed unifocal breast cancer planned for whole breast irradiation plus boost radiotherapy to the tumor bed. In both studies, a total dose of 40 Gy was applied to the whole breast and of 48 Gy to the tumor bed in 16 fractions of 2.5 and 3.0 Gy. Radiotherapy could be given either as three-dimensional conformal radiotherapy (3D-CRT) or as intensity-modulated radiotherapy (IMRT). The primary study objectives were feasibility and security within an observation period of six months. The current investigation focuses on long-term efficacy and toxicities.ResultsBetween 2011 and 2014, both trials enrolled 300 patients in total. Data from 274 of these patients could be used for the current analysis. The median follow-up time was 60 months and the 5-year disease-free survival 92.1%. Three patients suffered a local recurrence (after 36–72 months) while a regional recurrence occurred in one patient (after 17 months). The 5-year local control rate in the breast was 99.6%. 63.5% of all patients did not report any late radiation-related toxicity, 28.5% reported grade 1 and 7.3% grade 2 toxicities. The highest late toxicity was grade 3 in 2 women (0.7%, telangiectasia and lymphedema of the breast).ConclusionOur analysis demonstrates favorable efficacy and low rates of long-term side effects of HF with SIB after BCS. Randomized controlled phase III trials are ongoing.     

Outcomes with intraoperative radiation therapy for early‐stage breast cancer

Adjuvant radiation therapy has been associated with improved local control following breast‐conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3‐6 weeks or partial breast irradiation over 1‐3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early‐stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I‐II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x‐ray. Patients were treated at a single institution between 2011 and 2019. Follow‐up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow‐up of 23 months (range: 0‐73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor‐positive, 175 (87.9%) progesterone receptor‐positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low‐risk patients, demonstrated low rates of recurrence and reproducibility in a multi‐disciplinary setting. Further follow‐up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings.     

Preoperative radiotherapy of rectal cancer. The Lyons experience, 1985-1996. Prognostic study apropos of 312 patients

AIM OF STUDY: Preoperative radiotherapy is used increasingly in rectal cancer in Europe. This study is a retrospective analysis of a series of 312 patients with rectal adenocarcinoma treated by preoperative radiotherapy. MATERIAL AND METHOD: From 1985 to 1996, 312 patients were included in this study. Preoperative staging was: T2: 83, T3: 192 et T4: 21. On digital rectal examination, 25 patients were classified as N1. Endorectal sonographic staging was: uT1: 3, uT2: 77, uT3: 163, uN0: 122, uN1-2: 127. After surgery, pathological staging was: pT0: 43 (14%), pT1 24, pT2: 81, pT3: 151, pN0: 229, pN1-2: 81. Radiotherapy was delivered to the posterior pelvis with an accelerated schedule 39 Gy/13 fractions/17 days with x 18 MV. RESULTS: Median follow-up is 54 months. For pM0 patients (297 patients), the overall 5-year survival rate is 67%. Local failure rate is 9%. Since 1986, the rate of sphincter saving surgery is close to 65%. Various parameters related to the tumor were found to be significant prognostic factors on multivariate analysis in relation to 5-year overall survival rate: the T stage as judged by digital rectal examination and endorectal sonography, the N stage as evaluated on digital rectal examination but not with endorectal sonography. Pathological examination of the operative specimen retains a very strong prognostic value for pT and pN. CONCLUSION: Pathological examination of the specimen of rectal carcinoma retains a very strong prognostic value after preoperative radiation therapy. Endorectal sonography is of interest to evaluate T staging of the tumor but is not reliable for N stage.     

Fractionation in adjuvant radiotherapy for invasive breast cancer and ductal carcinoma in situ in Ontario,Canada from 2009 to 2015

The use of hypofractionated radiotherapy (HFRT) in patients with breast cancer and ductal carcinoma in situ (DCIS) in Ontario, Canada, from 2009 to 2015 was reported. A retrospective cohort study was conducted using data from the Institute for Clinical Evaluative Sciences (ICES). Patients with a breast cancer or DCIS diagnosis between 2009 and 2015 who received adjuvant breast or chest wall radiation were included. Trends in HFRT use (≤16 fractions) and factors associated with HFRT use in a multivariable logistic regression model with physician‐level random effect were reported. The approximate number of hours that could be saved if all patients were to receive HFRT was calculated. A total of 42 072 patients were included. All included characteristics were significantly associated with HFRT use. Hypofractionated radiotherapy use in patients with breast cancer and DCIS increased to around 75% in 2015. In stage I/II patients with mastectomy and chest wall radiation, HFRT use increased to 40% in 2015. Hypofractionated radiotherapy use in patients with regional nodal radiation or reconstruction has increased but remains under 20%. For breast cancer patients with breast‐conserving surgery (BCS) and breast radiation, 56 265 visits corresponding to 7200 hours of treatment or 3500 additional HFRT courses could have been saved. In conclusion, HFRT use in Ontario has increased in all patient populations but is nonuniform among physicians and institutions. Use of HFRT in chest wall and regional nodal radiation remains relatively lower than in breast cancer and DCIS patients with BCS.     

Preoperative Paclitaxel and Radiotherapy for Locally Advanced Breast Cancer: Surgical Aspects

Introduction: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer.Methods: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m² during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy.Results: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients.Conclusions: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.