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Purpose/objective(s) Cardiac radiation exposure is associated with an increased rate of adverse cardiac events in patients receiving radiation therapy for locally advanced non-small cell lung carcinoma (NSCLC). Previous analysis of practice patterns within the statewide Michigan Radiation Oncology Quality Consortium (MROQC) revealed 1 in 4 patients received a mean heart dose > 20 Gy and significant heterogeneity existed among treatment centers in using cardiac dose constraints. The purpose of this study is to analyze the effect of education and initiation of standardized cardiac dose constraints on heart dose across a statewide consortium. Materials/methods From 2012 to 2020, 1604 patients from 27 academic and community centers who received radiation therapy for locally advanced NSCLC were included in this analysis. Dosimetric endpoints including mean heart dose (MHD), mean lung dose, and mean esophagus dose were calculated using data from dose-volume histograms. These dose metrics were grouped by year of treatment initiation for all patients. Education regarding data for cardiac dose constraints was discussed in small lung cancer working group meetings and consortium-wide starting in 2016. This was followed in 2018 by implementation of a quality metric requiring mean heart dose Results Following education and implementation of the heart dose performance metric, mean MHD declined from an average of 12.2 Gy pre-intervention to 10.4 Gy post-intervention, and the percentage of patients receiving MHD > 20 Gy reduced by half. (Table). Mean lung dose and mean esophagus dose did not increase, and tumor coverage remained unchanged. Conclusion Education and implementation of a standardized cardiac dose quality measure across a statewide consortium was associated with a reduction of mean heart dose in patients receiving radiation therapy for locally advanced NSCLC. These dose reductions were achieved without sacrificing tumor coverage, increasing mean lung dose or mean esophagus dose. Analysis of the clinical ramifications of the reduction in cardiac doses is ongoing.

Background: We analyzed the risk of developing second malignancies in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) versus surgery alone (S). Material and Methods: The S+RT cohort consisted of 256 women treated with breast conserving therapy at William Beaumont Hospital. The S cohort consisted of 2,788 women with DCIS in the regional SEER database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 S patients (total of 2048 patients). Matching criteria included age +/− 2 years. The rates of second malignancies were analyzed overall and as contralateral breast versus non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the S cohort. The overall 10-/15-year rate of second malignancies among the S+RT and S cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the S cohort (p=0.439). The 15- year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the S alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and the S cohorts for pulmonary, gastrointestinal, central nervous system, gynecological, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Discussion: Compared with S alone, S +RT was not associated with an overall increased risk of second malignancies in women with DCIS. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-04.

BACKGROUND The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using interstitial brachytherapy. METHODS From April 1993 to December 2001, 199 patients with Stage I–II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at ≤ 6 months, 2 years, and 5 years. RESULTS The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95–99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years. CONCLUSIONS APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95–99% of patients and stabilized at 2 years. Cancer 2006. © 2006 American Cancer Society.

The authors reviewed changes in the initial clinical presentation, management techniques, and patterns of disease recurrence over time (1981-1996) in patients with breast carcinoma treated with breast-conserving therapy (BCT) at a single institution. The goals of the current study were to determine the frequency and use of optimal local and systemic therapy techniques and to evaluate the impact of these changes on treatment efficacy.Six hundred seven patients with American Joint Committee on Cancer Stage I or II invasive breast carcinomas treated with BCT at William Beaumont Hospital (Royal Oak, MI) constituted the study population. All patients received at least an excisional biopsy of the primary tumor, an axillary lymph node staging procedure, and postoperative radiotherapy (RT) (a median tumor bed dose of 61 Gray [Gy] was administered). All sides were reviewed by one pathologist. Numerous clinicopathologic and treatment-related factors were analyzed to monitor changes that occurred over time. Changes in patterns of disease recurrence and treatment efficacy over time also were analyzed.Over the time period analyzed, changes at initial presentation included an increase in the mean age at diagnosis (age 56.1 years vs. 61.4 years; P0.001), a decrease in the number of patients with clinically palpable tumors (78% vs. 36%; P0.001), a decrease in the mean tumor size (2.2 cm vs. 1.6 cm; P0.001), but no change in the percentage of patients with negative lymph nodes (79% vs. 78%; P = 0.83). No differences over time were observed in mean tumor grade (2.0 vs. 1.9; P = 0.2) or the presence of angiolymphatic invasion (27% vs. 26%; P = 0.25). Changes in surgical management and pathologic assessment included the more frequent use of reexcision (46% vs. 81%; P0.001), larger mean total volumes of breast tissue specimens excised (115 cm3 vs. 189 cm3; P = 0.001), a larger percentage of patients with final negative surgical margins (74% vs. 97%; P0.001), and a small increase in the mean number of lymph nodes excised (13.8 lymph nodes vs. 14.1 lymph nodes; P = 0.01). The only other significant change in the pathologic management of patients over time included a doubling in the mean number of slides examined (10.6 slides vs. 21.1 slides; P0.001). Changes in adjuvant local and systemic therapy included an increase in the percentage of patients treated with60 Gy to the tumor bed (66% vs. 95%; P0.001), a doubling in the mean number of days from the last surgery to the start of RT (24 days vs. 50 days; P0.001), and a decrease in the use of regional lymph node RT (24% vs. 8%; P0.001). The use of adjuvant tamoxifen increased from 10% to 61% (P0.001). Finally, improvements were observed in the 5-year and 12-year actuarial rates of local disease recurrence (8% vs. 1% and 21% vs. 9%, respectively; P = 0.001) and distant metastases (12% vs. 4% and 22% vs. 9%, respectively; P = 0.006). No changes in the mean number of years to ipsilateral (6.5 years vs. 6.4 years; P = 0.59) or distant disease recurrence (4.6 years vs. 3.8 years; P = 0.73) were observed.The impact of screening mammography and substantial changes in surgical, pathologic, RT, and systemic therapy recommendations were observed over time in the study population. These changes were associated with improvements in 5-year and 12-year local and distant control rates and suggested that improvements in outcome can be realized through adherence to best practice guidelines and continuous monitoring of treatment outcome data.

BACKGROUND The current study addressed two questions pertaining to lobular carcinoma in situ (LCIS) of the breast. First, does the risk of a subsequent carcinoma decrease over time after an LCIS biopsy and second, what is the clinical significance of E-cadherin-reactive LCIS? METHODS Eighty-two consecutive patients with a biopsy containing LCIS only, no prior history of breast carcinoma, and follow-up information available for the period 1955–1976 were reviewed. No patients underwent a mastectomy for LCIS. Four hundred eighty-six sections were stained with E-cadherin. E-cadherin reactivity was correlated with clinicopathologic features of the LCIS and subsequent tumors. The mean number of blocks stained per case was 5.9. The mean follow-up period was 21.6 years. RESULTS Sixteen patients (19.5%) developed 21 subsequent invasive carcinomas (9 ipsilateral, 2 contralateral, and 5 bilateral carcinomas). The 10-year and 20-year actuarial rates of developing subsequent carcinoma were 7.8% and 15.4%, respectively. Six of the 21 carcinomas (29%) developed after 20 years. Nine LCIS cases (10.9%) had focal E-cadherin reactivity. When compared with patients with nonreactive LCIS, patients with E-cadherin-reactive LCIS more frequently developed a subsequent ipsilateral carcinoma that had a ductal component (55.5% vs. 12.3%; P < 0.01). The subsequent carcinomas also developed after significantly shorter time periods (mean of 7.6 years vs. 19.6 years; P < 0.01). CONCLUSIONS LCIS appears to confer a persistent, increased risk of subsequent breast carcinoma that does not appear to decrease over time. E-cadherin reactivity appears to identify a subset of LCIS patients with risk factors for subsequent carcinoma similar to those of patients with low-grade intraductal carcinoma. Cancer 2001;92:738–47. © 2001 American Cancer Society.

BACKGROUND The authors reviewed their institution's experience treating patients with mammographically detected ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine 10-year rates of local control and survival and to identify factors associated with local recurrence. METHODS From January 1980 to December 1993, 132 breasts in 130 patients were treated with BCT for mammographically detected DCIS at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent an excisional biopsy, and 64% were reexcised. All patients received postoperative whole-breast irradiation to a median dose of 45.0 Gray (Gy) (range: 43.1–56.0 Gy). One hundred twenty-four cases (94%) received a boost to the tumor bed for a median total dose of 60.4 Gy (range: 45.0–71.8 Gy). All cases underwent complete pathologic review by one pathologist. The median follow-up was 7.0 years. RESULTS Of the entire study group, 13 patients developed recurrence within the ipsilateral breast, for 5- and 10-year actuarial rates of 8.9% and 10.3%, respectively. Nine of the 13 recurrences (69%) occurred within or immediately adjacent to the lumpectomy cavity and were designated as true recurrences or marginal misses (TR/MM). Four patients (31%) had recurrence elsewhere in the breast. Ten of the 13 recurrences (77%) were invasive, whereas 3 (23%) were pure DCIS. Only 1 patient died of disease, corresponding to 5- and 10-year actuarial cause specific survival rates of 100% and 99.0%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with ipsilateral breast failure or TR/MM. In multivariate analysis, only the absence of pathologic calcifications was significantly associated with ipsilateral breast failure. When specifically analyzed for TR/MM, younger age at diagnosis, number of slides with DCIS, number of DCIS and cancerization of lobules (COL) foci within 5 mm of the margin, and the absence of pathologic calcifications demonstrated a statistically significant association. Close or positive margin status did not significantly predict for either TR/MM (P = 0.14) or ipsilateral breast failure (P = 0.19). CONCLUSIONS In patients with mammographically detected DCIS treated with BCT, adequate excision of all DCIS prior to RT can result in improved rates of local control. However, margin status may not adequately predict complete tumor extirpation. The volume of DCIS within 5 mm of the margin appears to be a more reliable surrogate for the adequacy of excision. In addition, young patient age and the absence of pathologic calcifications are independent risk factors for the development of local recurrence. Cancer 2000;88:596–607. © 2000 American Cancer Society.

BACKGROUND. The authors retrospectively reviewed their institution's long term experience treating a group of comparably staged low risk prostate carcinoma patients with either radical prostatectomy or external beam radiation therapy (RT) to determine whether the method of treatment resulted in significant differences in biochemical control and/or survival. METHODS. From January of 1987 through December of 1994, 382 patients (157 who underwent radical prostatectomy and 225 who received external beam RT) were treated with curative intent for localized prostate carcinoma at William Beaumont Hospital. All patients had a pretreatment serum prostate specific antigen (PSA) level ≤ 10.0 ng/mL and a biopsy Gleason score ≤6. Patients treated with RT received a median dose of 66.6 gray (Gy) (range, 59.2-70.2 Gy) to the prostate. Patients treated surgically underwent radical retropubic prostatectomy with a pelvic lymph node dissection. For surgical patients, biochemical failure was defined as a detectable PSA level ≥0.2 ng/mL at any time after prostatectomy. For RT patients, biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Pretreatment PSA levels and Gleason scores were not significantly different between patients treated with radical prostatectomy or RT. The median follow-up in each treatment group was 5.5 years. RESULTS. The 7-year actuarial rates of biochemical control and cause specific survival were not significantly different between patients treated either with radical prostatectomy or RT (67% vs. 69% for biochemical control and 99% vs. 97% for cause specific survival, respectively). A number of clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical failure (i.e., age, pretreatment PSA, Gleason score, and treatment modality). Only pretreatment PSA and Gleason score were significantly related to outcome in both univariate and multivariate analyses. CONCLUSIONS. Low risk prostate carcinoma patients with similar pretreatment PSA levels and biopsy Gleason scores treated at the same institution with either radical prostatectomy or RT achieved similar 7-year rates of biochemical control and cause specific survival, regardless of treatment technique. These findings suggest that for patients with pretreatment PSA levels ≤10 ng/mL and Gleason scores ≤6, conventional doses of external beam RT and radical retropubic prostatectomy can be expected to produce comparable treatment results unaffected by age at diagnosis.

OBJECTIVES We analyzed differences in disease presentation, outcomes, and toxicities between African American (AA) and White (W) men treated with definitive radiation therapy for their prostate cancer. METHODS Three thousand one hundred eighty cases of prostate cancer treated with various radiation modalities at a single institution were reviewed. The cohort consisted of 92% W patients and 8% AA patients. Clinical and pathologic characteristics at presentation, treatment outcomes, and related toxicities were analyzed between the 2 groups. The median follow-up was 6.6 years (0.6 to 22.4 y). RESULTS At presentation, AA men were younger (P

To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT).Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%,1%, 1-10%, or10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints.Median follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (1% n = 21, 1-10% n = 11,10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with1% vs.1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs.1% NED.For Gleason score 8-10 prostate cancer,1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.

Aims To evaluate outcomes after treatment with image-guided stereotactic body radiation therapy (SBRT) using daily online cone beam computed tomography for malignancies metastatic to the lung. Materials and methods Forty-seven lung metastases in 32 patients were treated with volumetrically guided SBRT. The median age was 62 years (21–87). Primaries included colorectal ( n = 10), sarcoma ( n = 4), head and neck ( n = 4), melanoma ( n = 3), bladder ( n = 2), non-small cell lung cancer ( n = 2), renal cell ( n = 2), thymoma ( n = 2), thyroid ( n = 1), endometrial ( n = 1) and oesophageal ( n = 1). The number of lung metastases per patient ranged from one to three (68% single lesions). SBRT was prescribed to the edge of the target volume to a median dose of 60 Gy (48–65 Gy) in a median of four fractions (four to 10). Most lesions were treated using 12 Gy fractions (92%) to 48 or 60 Gy. Results The median follow-up was 27.6 months (7.6–57.1 months). The 1, 2 and 3 year actuarial local control rates for all treated lesions were 97, 92 and 85%, respectively. Two patients with colorectal primaries (four lesions in total) had local failure. The median overall survival was 40 months. The 1, 2 and 3 year overall survival from the time of SBRT completion was 83, 76 and 63%, respectively. There were no grade 4 or 5 toxicities. Grade 3 toxicities (one instance of each) included pneumonitis, dyspnoea, cough, rib fracture and pain. Conclusion SBRT with daily online cone beam computed tomography for lung metastases achieved excellent local tumour control with low toxicity and encouraging 2 and 3 year survival.

(SUVmax) in the pretreatment setting, but other metrics of FDG avidity are possible and may be more predictive, either in the preor post-CRT setting. We therefore evaluated the association of multiple preand postCRT PET metrics with outcomes in LS-SCLC. Materials/Methods: We identified 79 LS-SCLC patients who had fully analyzable PET-CT data either before or after CRT. Sixty-seven patients had analyzable pre-CRT PET data, and 35 had analyzable post-CRT PET data. All patients received chemotherapy, mostly concurrently with radiation therapy (84%). Forty-nine patients received twice-daily radiation (median 45 Gy), while 30 patients received oncedaily radiation (median 54 Gy). All scans were independently reanalyzed by a nuclear medicine physician. Using region of interest analysis, SUVmax, mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated for the index lesion in each patient. Kaplan-Meier analysis was used to evaluate overall survival (OS), locoregional failure-free survival (LFFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). The log-rank test was used to assess correlation between survival and the PET-CT metrics. Results: Median follow-up was 19 months, and OS of the whole cohort was 50% at 2 years and 21% at 5 years. With respect to pre-CRT PET, neither SUVmax, SUVmean, MTV nor TLG were significantly associated with any endpoint, nor was there any trend in that direction. With respect to post-CRT PET, a significant association was seen between higher residual MTV and worse DFS (p Z 0.026), but not with LFFS, DMFS or OS. No other significant associations with post-CRT PET metrics were identified. Conclusions: By analyzing multiple PET metrics in both preand postCRT settings, this study presents a comprehensive attempt to identify correlation between FDG avidity and outcome in LS-SCLC. A significant association between post-CRT metabolic tumor volume and disease-free survival was observed, but this finding is difficult to interpret given the lack of significant or near-significant correlations in other analyzed interactions of survival and FDG avidity. Prospective evaluation in a larger cohort may be more revealing; however, this study suggests that PET is unlikely to provide meaningful prognostic information in LS-SCLC patients treated with CRT. Author Disclosure: L. Ong: None. C.A. Perez: None. A. Foster: None. M.C. Pietanza: None. K. Rosenzweig: None. D.Y. Gelblum: None. M.P. Dunphy: None. A. Rimner: G. Consultant; General Electric. A.J. Wu: None.

Materials/Methods: Ninety-five patients underwent GK for TGN between 12/2006-6/2009 at William Beaumont Hospital. Eighty had follow-up $6 weeks and were the subject of this report. Median patient age was 68y (30-92); 58 female, 22 male. 74% of patients had typical trigeminal pain, 11% atypical features and 11% multiple sclerosis. Thirty patients (38%) had undergone prior surgical procedures and 37 (46%) had preexisting sensory complaints. The median dose delivered was 40 Gy (range: 35-45 Gy) to the 50% isodose line (80 Gy max) using either a single (85%) or two (6%) isocenters with a 4 mm collimator, or two isocenters with a 4 and 8 mm collimator (9%). Patients were seen #2 weeks post-GK, then every 3-6 months in addition to periodic mail surveys and telephone interviews. Pain was evaluated using the Barrow Neurological Institute Pain Intensity Scale. Multiple patient and GK factors were analyzed for association with pain relief. Mean follow-up duration was 15.6 months.