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BackgroundThere are limited data on accelerated partial breast irradiation (APBI) using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC) are suitable for APBI.MethodsThe retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC), ILC, or Tis (DCIS) treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF) was pathologically confirmed as a local failure (LF) or an elsewhere failure (EF).ResultsMedian follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9%) including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent.ConclusionsExternal beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not differentiate a subset of patients with a higher rate of IBF. APBI may be an appropriate treatment for women with DCIS and ILC.

Between 1975 and 1980,101 patients with inoperable Stage IIIMO non‐small cell lung carcinoma were entered into combined radiotherapy and chemotherapy trials at Michael Reese Hospital and University of Chicago Hospital. Sixty‐four percent of the patients responded. Median survival for all patients was 8.8 months, Responders survived 13.7 months and nonresponders 4.6 months (P = 0.002). Patients treated with 4200 rad had a higher response rate than those treated with 3Ooo rad (74% versus 54%, P = 0.04) but there was no difference in survival. Although all patients with squamous cell carcinoma died by 30 months, 18% of patients with adenocarcinoma and 20% of patients with large cell carcinoma are long‐term survivors. Brain metastases occurred more frequently in patients with large cell or adenocarcinoma than in patients with squamous cell carcinoma (P = 0.02). The prognostic effect of age, initial performance status, sex, histology, and tumor extent are examined. Toxicity was substantial with a 13% treatment‐related mortality. Combined modality therapy may benefit selected patients with non‐squamous cell types, but more effective chemotherapeutic agents are needed. Prophylactic cranial irradiation in patients with large cell carcinoma or adenocarcinoma may decrease the incidence of subsequent brain metastases.

IBTR rates were higher in external beam APBI group compared with WBI, but APBI had fewer toxicities. Clinicians must weigh the risks and benefits of APBI when making a recommendation for partial breast irradiation after lumpectomy.

The primary induction of lung cancer is difficult to study in humans because patients often present very late in the course of their disease. Genetically engineered mouse models (GEMMs) have therefore emerged as crucial bridging strategies between understanding pathogenic mechanisms and clinical translation. Importantly, they reveal insights on the events and processes underlying tumor initiation and progression, studies which are not possible when employing transplantation or chemically-induced model systems. The recent advent of next-generation sequencing technologies has provided us with an indepth characterization of the cancer genome of lung adenocarcinoma (LUAD) (1), squamous cell carcinoma (LUSC) (2) and small cell lung cancer (SCLC) (3). While these studies have highlighted the genetic complexities of lung cancers, attention is now focused on elucidating "driver" mutations that confer a growth advantage, from "passenger" mutations that have little impact on malignant transformation. Investigating the loss or gain-of-function of individual genes, alone or in combination, can be directly addressed using GEMM systems. The "gold-standard" lung cancer models are based on Cre-LoxP recombination technology that enable the formation of autochthonous tumors from a limited number of somatic cells in a spatial and temporal fashion. Critically, tumors arise sporadically within the lung, in the setting of an intact immune microenvironment. GEMMs are designed to harbor genetic mutations frequently identified in human lung cancer. Cre-inducible alleles are engineered to disrupt tumor suppressor genes (LoxP sites flanking key exons (floxed), that are removed upon recombination) and/or activate oncogenes (LoxPflanked stop codons (lox-stop-lox) that result in gene expression upon recombination). Cre-recombinase is delivered to the lung via inhalation or intra-tracheal injection of a recombinant adenovirus (Ad5) expressing Cre-recombinase under the control of a ubiquitous cytomegalovirus (CMV) promoter. Expression of Cre-recombinase directs the recombination of floxed alleles in a variety of epithelial cell types in the adult mouse lung (4,5). Utilizing this approach enabled investigators to interrogate the functional consequences of genetic alterations found in human lung cancer through the generation of models of LUAD, SCLC and more recently lung LUSC (6). Moreover, the recent advent of CRISPR-Cas9 gene-editing technology now enables us to interrogate the functional interaction between multiple genetic alterations in a high-throughput setting (7). Furthermore, the generation of cell type specific Ad5-Cre viruses, that restrict Cre expression, and thus recombination, to alveolar type II (ATII) (Ad5-SPC-Cre), club (Ad5-CC10-Cre), neuroendocrine (Ad5-CGRP-Cre) and basal (Ad5-K5-Cre, Ad5-K14-Cre) (8) cells, have provided insights into the cellular origins of different subtypes of lung cancer (9,10). Critically, unlike patient-derived xenograft (PDX) models, one additional advantage of GEMMs is the ability to interrogate the i...