Randomized trials have demonstrated similar local tumor control in patients treated with APBI compared to whole breast radiation. However, the optimal APBI dose for optimizing tumor control and minimizing toxicity is uncertain. We present 10-year results from a phase I-II dose-escalation trial. Patients of any age with grade 1 or 2 DCIS or stage I invasive breast cancer, and resection margins ≥2 mm, were treated with 3D-conformal external-beam APBI using twice-daily 4 Gy fractions. They were sequentially accrued to three dose cohorts (32 Gy, 36 Gy and 40 Gy) between 2003 and 2011. Most were irradiated using mini-tangents plus en-face electrons (not exceeding 20% of the dose), or 3-4 coplanar photon beams; 19 patients in the first dose cohort were treated with protons. The planning target volume (PTV) was defined by expanding the cavity by 1.5–2 cm, limited anteriorly to 5 mm below the skin surface and posteriorly to the anterior chest wall or pectoralis muscle. Follow-up included questionnaire-based assessments of cosmesis and toxicity by both patients and physicians semiannually for the first five-years and annually thereafter. Actuarial analysis was used to report 10 years cumulative incidence rates and multivariate cox models investigated significant dosimetric factors associated with toxicity outcomes. The trial accrued 324 patients (99, 101, and 124 for 32, 36 and 40 Gy cohorts, respectively). Median follow-up was 8 years. The median PTV/breast volume ratio was 18% (interquartile range, 14-22%). There were 11 local failures, 5 of them elsewhere recurrence, and two arose >10 years after treatment (one each in the 32 Gy and 36 Gy arms). The 10-year cumulative incidence of local failure in each dose cohort was 5.2%, 5.2% and 2.2%, respectively (log-rank p = 0.2). The 10-year cumulative incidence of contralateral breast cancer was 7.3%, 6.6% and 6.6%, respectively (log-rank p = 0.6). The 10-year rate of moderate or severe fibrosis by physician assessment was 37%, 52% and 66.7%, respectively (log-rank p<0.01). The 10-year actuarial rate for fair or poor cosmetic appearance reported from patients was 22.8%, 30.5%, and 45%, respectively (log-rank p<0.01). Physician assessment for fair or poor cosmesis yielded similar 10-year actuarial risk of 20.7%, 36%, 45.3%, respectively (log-rank p<0.01). Multivariate analysis found that the percentage of the dose delivered with electrons and the PTV volume receiving 95% of the total dose (V95%) were significantly associated with the risk of fibrosis. There were no significant differences in local failure rates between 32 Gy, 36 Gy or 40 Gy delivered in twice-daily 4-Gy fractions. However, rates of moderate or severe fibrosis and worse cosmetic outcome significantly increased for patients treated to the two higher doses. These findings suggest that 32 Gy in 8 fractions may be an optimal dose for appropriate patients when APBI is administered using twice daily fractionation.

The absence of real-time, detailed, 3D information on the composition of surgical specimens presents an enormous challenge in surgical oncology and pathology.

Post-Mastectomy Radiation Therapy (PMRT) improves outcomes for women with locally advanced breast cancer (LABC). Although standard RT is generally well tolerated, cardiopulmonary toxicity is a concern for selected patients with unfavorable anatomy. This pilot trial assesses the feasibility of delivering proton PMRT for LABC. The intent of this study is to exploit the properties of protons for delivery of PMRT without need for removal or manipulation of breast reconstruction and/or to decrease cardiac exposure to radiation and to document acute and late toxicities. All patients were enrolled on an IRB approved trial and treated between August 2011 and February 2012 . All met criteria for unfavorable anatomy based on diagnostic computed tomography scan (CT). All patients underwent CT planning scans with free breathing and breath hold techniques for dosimetric comparison. Contrast was administered for better visualization of cardiac anatomy. Strain echocardiograms were obtained prior to treatment and at 4 and 8 week's post-radiation. All patients agreed to photographs to document skin reaction. Nine patients with LABC (T2/T3, N1-N3) were enrolled following mastectomy +/- reconstruction. All patients received chemotherapy prior to radiation. A dose of 50.4 Gy (RBE) was delivered to the chest wall and 45-50.4 Gy (RBE) was delivered to the regional lymphatics at risk. All patients received the entire RT course with protons using two en face fields, matched and feathered. Median elapsed days for RT delivery was 42 (range 38-45). Average mean dose to the heart, left ventricle, and lung was 0.44, 0.09, and 6 Gy(RBE), respectively. Average V20 to the heart, lung, and left ventricle was 0%, 0%, and 13%, respectively. Maximum CTCAE skin toxicity during RT was grade 2 and maximum CTCAE fatigue was grade 3. There were no cases of radiation pneumonitis. Delivery of proton radiation was feasible and well tolerated. Protons provide excellent sparing of cardiopulmonary structures in the setting of complex anatomy due to poor cardiac anatomy and/or breast reconstruction.

Determine the optimal dose for patients treated with 3D-APBI using twice-daily fractions of 4 Gy. From October 2003 to September 2009, 323 patients were treated on a Phase I multi-institutional IRB-approved dose-escalation trial. All patients gave written informed consent. The prescribed doses in the three cohorts were 32 Gy (98 pts), 36 Gy (100 pts), and 40 Gy (125 pts). Eligibility criteria included: tumor 2 cm or smaller; infiltrating ductal histology or special subtype; pN0; no EIC or LVI; margins 2 mm or wider. Patients with DCIS grade 1 or 2 were eligible for the second and third cohorts. The excision cavity was expanded by 1.5-2 cm to create the planning target volume (PTV), which was then edited to come no closer than 5 mm to the skin surface and no deeper than the anterior chest wall or pectoralis muscles. Treatment was given with mixed photons and electrons (262 pts), photons alone (41 pts), or protons (20 pts). Median follow-up was 52 months (76 months, 56 months, and 36 months in the three cohorts, respectively). The median age was 61 years (range, 40-87 years); the median tumor size was 0.8 cm; 23% had DCIS, 93% of tumors were ER+. Seven of 325 pts (2%) had ipsilateral recurrence: 5 (5%) in the 32 Gy cohort; 2 (2%) in the 36 Gy cohort; and none in the 40 Gy cohort. Four-year local recurrence rates were 3%, 1%, and nil, respectively. Overall cosmesis at last follow-up was excellent or good in 88%, 81% and 86% of the 3 cohorts, respectively, as assessed by the physician (p = 0.12) and 94%, 94% and 82% as assessed by the patient (p = 0.0006). The incidence of fat necrosis at last follow-up was 6%, 8% and 13%, respectively (p = 0.2). Moderate fibrosis at last follow-up was found in 17%, 22% and 30% of pts, respectively (p = 0.03). This dose-escalation study resulted in low local failure rates in all 3 cohorts, with increased risks of fibrosis and fat necrosis in the 40 Gy cohort, despite shorter follow-up. If confirmed by longer follow-up, this suggests that 36 Gy may be the maximum tolerated dose for 3D-APBI when giving 4-Gy fractions twice daily.

Le traitement conservateur des carcinomes canalaires in situ du sein repose sur la tumorectomie suivie d’une irradiation mammaire. L’impact d’un complément d’irradiation au niveau du lit opératoire est en cours d’évaluation.Étude rétrospective d’une cohorte monocentrique incluant l’ensemble des patientes atteintes d’un carcinome canalaire in situ traité par tumorectomie suivie de radiothérapie externe de 45 Gy et complément de 15 Gy entre 1990 et 2008.Cent soixante et onze patientes ont été incluses. Le suivi médian était de 95,1 mois. Le complément d’irradiation du lit opératoire a été administré par une technique de curiethérapie interstitielle pour 66 patientes (39 %), par un faisceau direct d’électrons pour 86 (50 %) et par des faisceaux tangentiels de photons pour 19 (11 %). Huit rechutes locales (4,6 %) ont été observées. Le taux de survie sans rechute locale était de 97 % à 10 ans. Le taux de survie globale à 10 ans était de 98 %. Après analyse multifactorielle, la curiethérapie (p = 0,05 ; hazard ratio = 5,15 ; intervalle de confiance = 1–26,3) était un facteur significatif de réduction du taux de survie sans rechute locale.Dans notre expérience, l’irradiation mammaire suivie d’un complément dans le lit opératoire a permis d’obtenir un taux de survie sans rechute locale à 10 ans élevé.Women with ductal carcinoma in situ are treated with breast-conserving surgery and radiation therapy. The impact of an additive boost radiation is under evaluation.All 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.We 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.In 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.

O'Toole, J.; Russell, T.; Specht, M.; Ancukiewicz, M.; Murphy, C.; Singer, M.; Smith, B.; Taghian, A. Author Information

Purpose: Early identification of the disease severity in acute pancreatitis and focused management based on Ranson's criteria has shown to improved patients’ outcomes in many trials. We introduced Ranson's criteria at Ipswich Hospital in 2007 and compared the patients’ outcome using historical controls. Methodology: A retrospective chart analysis was undertaken on patients diagnosed with acute pancreatitis at Ipswich Hospital between 2006 and 2007. Ranson's criteria and treatment protocols were introduced in January 2007 and data was collected prospectively. Data was assessed for the length of hospital stay, ICU admission, transfers to tertiary centres, morbidity and mortality. Results: 33 patients were admitted with acute pancreatitis in 2006 compared to 76 patients in 2007. Ranson's criteria were not formally assessed in any patient prior to 2007. However, 88% of patients had Ranson's criteria scored with strict adherence to the treatment protocol since 2007. 13 patients were scored as severe (greater than 3) in 2007 compared to none in 2006. 6% of patients developed pneumonia compared to 14% in 2007. Length of stay was 5.5 days in 2007 versus 4.87 days in 2006. Five ICU admissions and 4 transfers to tertiary centres occurred in 2007 compared to one transfer with no ICU admissions in 2006. There was no mortality in 2006 compared to 2% in 2007. Conclusion: Use of Ranson's criteria enables us to tailor our treatment of acute pancreatitis. It is a clinically useful tool and strict adherence leads to quick severity stratification, improved management and better use of health care resources.

Multiple re-excisions are often necessary after initial lumpectomy to obtain negative margins for breast conservation therapy. If a first re-excision still yields positive margins, the patient and surgeon have to decide whether to proceed with a second re-excision or convert to mastectomy, even though evidence on recurrence based on either decision is limited. This study addresses whether converting to mastectomy to obtain negative margins after one or more re-excisions results in a difference in locoregional recurrence (LRR) compared to continued re-excisions. A retrospective analysis of 186 patients with Stage 1-2 breast cancer treated between 1980 and 2005 at Massachusetts General Hospital was performed. Patients were divide into two groups: group A) 1 or more re-excisions followed by mastectomy to obtain negative margins (119 cases), and group B) 2 or more re-excisions with no mastectomy (67 cases) to achieve clear margins. Median follow-up was the same for both groups A and B (90 months). There was no difference in age, tumor size, nodal status, lymphovascular invasion, ER/PR status, or adjuvant chemotherapy between the two groups. Final margins were clear (>0.2cm) in 97% and 99% of patients in each group. The percent of patients in Group A who had 1, 2, or 3 re-excisions before mastectomy was 78%, 21%, and 1%, respectively. In Group B, the percent of patients with 2 or 3 re-excisions was 93% and 7%. Proportion of LRR was higher in Group B versus A (6/67 cases vs. 3/119, p=0.05). On Cox proportional hazards analysis of time to LRR the difference did not quite reach statistical significance (p = 0.06, Log Rank test). There is no difference for distant failures between Group A and B. Univariate Cox analysis of the entire cohort of 186 patients identified premenopausal status (p = 0.03), poor grade (p = 0.02), younger age (p = 0.05) and Her2+++ status (p = 0.0002) as risk factors for local failure. While there is an indication that having more than one re-excision is associated with increased risk of local failure relative to a single re-excision followed by mastectomy, it is not statistically significant (p = 0.09). Among early stage breast cancer patients with positive margins after a single re-excision, those who ultimately convert to mastectomy to obtain clear margins may have a lower rate of LRR compared to those who have re-excisions as a final treatment to obtain negative margins. However, there is no difference in survival between the two groups of patients. Evaluation of larger, better-powered cohorts may help further inform the clinical decisions for these patients.

There has been much uncertainty as to whether metastasis requires mutation at the time of spread. Here, we use clinical data to calculate the probability of the spread of melanoma and breast cancer cells. These calculations reveal that the probability of the spread of cancer cells is relatively high for small tumours (∼1 event of spread for every 500 cells for melanomas of 0.1 mm) and declines as tumours increase in size (∼1 event of spread for every 10 8 cells for melanomas of 12 mm). The probability of spread of breast cancer cells from the lymph nodes to the periphery is ∼1 event of spread for every 10 8 cells in the nodal masses, which have a mean diameter of 5 mm, while the probability of spread of cancer cells from the breast to the periphery when the primary masses are 5 mm is also ∼1 event of spread for every 10 8 cells. Thus, the occurrence of an event of spread from the breast to the lymph nodes appears not to increase the propensity of the progeny of those cells to spread from the lymph nodes to the periphery. These values indicate that the spread of human breast cancer and melanoma cells is unlikely to occur by a mechanism requiring mutation at the time of spread.