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Purpose Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR. Methods and Materials This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiotherapy without bolus or beam spoilers. The primary endpoint was the cumulative incidence of LR (CILR). A multivariable analysis (MVA) included mean beam energy, age, T-stage, nodal status, overall stage, lymphovascular invasion (LVI), grade, margin status, extensive intraductal component (EIC), breast cancer subtype, hormone therapy and chemotherapy. In a subgroup with contoured surgical beds, another MVA included surgical bed-to-skin distance. Results The cohort consisted of 10,083 women treated from 2002 to 2011, 327 with 4MV, 6,006 with 6 MV, 2,083 with >6-10 MV and 1,667 with >10 MV tangents. The median follow-up time was 11.1 years. The 10-year CILR was 3.1% [95% confidence interval 1.6,5.4] with 4 MV, 2.8% [2.4,3.3] with 6 MV, 4.2% [3.4,5.3] with >6-10 MV and 2.6% [1.9,3.5] with >10 MV. On MVA of the entire cohort, LR risk was increased with positive margins, LVI, EIC, and lack of hormone therapy, but was not associated with beam energy (HR = 1.01 [0.96,1.05], p = 0.8). On MVA of 3,359 patients with contoured surgical beds, LR risk was not associated with surgical bed-to-skin distance (HR = 1.00 [0.99,1.02], p = 0.8). Conclusions Use of higher breast tangent beam energies is not associated with increased risk of local recurrence, including in cases with surgical beds that are close to the skin.

Purpose Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement. Methods and Materials For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011. Eligible patients had newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with adjuvant or neoadjuvant radiation therapy. For the bolus and no-bolus groups, we compared the cumulative incidence of local recurrence (LR) and locoregional recurrence (LRR) with distant recurrence and death as competing risks and breast cancer mortality (BCM). Multivariable analysis of LR and BCM included stage, subtype, lymphovascular invasion, grade, margin status, beam energy, bolus use, hormone therapy, chemotherapy, and reconstruction. Results Systemic therapy was used for 98% of the 1887 patients. The bolus group had 1569 patients and the no-bolus group had 318 patients. Bolus was used in 51% (281/550) of patients treated with reconstruction and 96% (1288/1337) of patients treated without reconstruction. The 10-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: LR 1.9% (1.3-2.7) versus 0.9% (0.3-2.6), LRR 3.1% (2.3-4.0) versus 3.2% (1.6-5.5), and BCM 19.4% (17.3-21.6) versus 18.3% (13.9-23.2). On multivariable analysis, bolus use was not associated with better LR (hazard ratio = 1.4 [0.3-6.4]) or BCM (hazard ratio = 0.8 [0.5-1.2]). Conclusions For patients treated with mastectomy, radiation therapy, and modern systemic therapy, the cumulative incidence of LR was low, with or without bolus. Because bolus use increases toxicity and does not reduce LR or BCM, it should no longer be used routinely for patients without skin involvement who receive systemic therapy.

Purpose This study evaluated long-term, population-based, breast cancer–specific outcomes in patients treated with radiation therapy (RT) to the breast/chest wall plus regional nodes using hypofractionated (HF) (40-42.5 Gy/16 fractions) versus conventionally fractionated (CF) regimens (50-50.4 Gy/25-28 fractions). Methods and Materials A prospective provincial database was used to identify patients with lymph node–positive breast cancer treated with curative-intent breast/chest wall + regional nodal RT from 1998 to 2010. The effect of RT fractionation on locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and breast cancer–specific survival (BCSS) was assessed for the entire cohort and for high-risk subgroups: grade 3, ER–/HER2–, HER2+, and ≥4 positive nodes. Multivariable analysis and 2:1 case-match comparison of HF versus CF were also performed. Results A total of 5487 patients met the inclusion criteria (4006 HF and 1481 CF). Median age was 55 years, and median follow-up was 12.7 years. On multivariable analysis, no statistically significant differences were identified in 10-year LRRFS (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.59-1.27; P = .46), DRFS (HR 0.90; 95% CI, 0.76-1.06; P = .19), or BCSS (HR 0.92; 95% CI, 0.76-1.10; P = .36) between the HF and CF cohorts. There was no statistical difference in breast cancer–specific outcomes in the high-risk subgroups. On analysis of 2962 HF cases matched to 1481 CF controls, no statistical difference was observed in LRRFS (HR 0.98; 95% CI, 0.71-1.33; P = .87), DRFS (HR 0.97; 95% CI, 0.85-1.11; P = .68), or BCSS (HR 1.00; 95% CI, 0.87-1.16; P = .92). Conclusions This large, population-based analysis with long-term follow-up after locoregional RT demonstrated that modest HF provides similar breast cancer–specific outcomes compared with CF. HF is an effective option for patients with stage I to III breast cancer receiving nodal RT.

The optimal treatment for patients with extensive pure ductal carcinoma in situ (DCIS) ≥4 cm is controversial. This study evaluates local relapse according to type of local therapy: mastectomy, breast-conserving surgery (BCS) alone, and BCS + radiation therapy (RT).Subjects were female patients who received diagnoses of pure DCIS ≥4 cm between 1989 and 2010 and were referred to British Columbia Cancer. Clinicopathologic and treatment characteristics were compared between treatment cohorts. Local relapse (LR) was estimated using competing risk analysis. Multivariable analysis was performed using Cox regression analysis.Patients had the following treatments: 490 mastectomy, 38 BCS alone, and 192 BCS + RT. The 10-year cumulative incidence of LR was 16% after BCS (95% confidence interval [CI], 6-29%), 8% after BCS + RT (95% CI, 4-12%), and 2% after mastectomy (95% CI, 1-4%). On multivariable analysis, estrogen receptor-negative disease (hazard ratio [HR], 3.32; 95% CI, 1.08-10.18; P = .04) and positive margins (HR, 3.55; 95% CI, 1.56-8.05; P = .002) were associated with increased LR. BCS alone (HR, 7.87; 95% CI, 2.82-21.92; P .0001), BCS + RT + no boost (HR, 3.80; 95% CI, 1.56-9.28; P = .003), and BCS + RT + boost (HR, 5.76; 95% CI, 2.59-12.83; P .0001) were all associated with a higher risk of relapse relative to mastectomy.Mastectomy remains a standard local treatment option for extensive DCIS, but BCS + RT may also be reasonably considered in selected patients with a careful discussion of the benefits, side effects, and patient preferences.

To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx.Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χOf 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy.Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

The 2014 Society of Surgical Oncology-American Society for Radiation Oncology consensus suggested "no ink on tumor" is a sufficient surgical margin for invasive breast cancer treated with breast-conserving surgery (BCS). Whether close margins2 mm are associated with inferior outcomes remains controversial. This study evaluated 10-year outcomes by margin status in a population-based cohort treated with BCS and adjuvant radiation therapy (RT).The subjects were 10,863 women with invasive cancer categorized as pT1 to T3, any N, and M0 referred from 2001 to 2011, an era in which the institutional policy was to re-excise close or positive margins, except in select cases. All women underwent BCS and whole-breast RT with or without boost RT. Local recurrence (LR) and breast cancer-specific survival (BCSS) were examined using competing-risk analysis in cohorts with negative (≥2 mm; n = 9241, 85%), close (2 mm; n = 1310, 12%), or positive (tumor touching ink; n = 312, 3%) margins. Multivariable analysis and matched-pair analysis were performed.The median follow-up period was 8 years. Systemic therapy was used in 87% of patients. Boost RT was used in 34.1%, 76.9%, and 79.5% of patients with negative, close, and positive margins, respectively. In the negative, close, and positive margin cohorts, the 10-year cumulative incidence of LR was 1.8%, 2.0%, and 1.1%, respectively (P = .759). Corresponding BCSS estimates were 93.9%, 91.8%, and 87.9%, respectively (P .001). On multivariable analysis, close margins were not associated with increased LR (hazard ratio, 1.25; 95% confidence interval 0.79-1.97; P = .350) or reduced BCSS (hazard ratio, 1.25; 95% confidence interval 0.98-1.58, P = .071) relative to negative margins. On matched-pair analysis, close margin cases had similar LR (P = .114) and BCSS (P = .100) to negative margin controls.Select cases with close or positive margins in this population-based analysis had similar LR and BCSS to cases with negative margins. While these findings do not endorse omitting re-excision for all cases, the data support a policy of accepting carefully selected cases with close margins for adjuvant RT without re-excision.

To prospectively capture acute toxicities and pain associated with postmastectomy radiation therapy (PMRT), to analyze patient and treatment risk factors for severe side effects.Women referred for PMRT were prospectively enrolled and assessed weekly during and after radiation therapy. The endpoint included severe National Cancer Institute Common Terminology Criteria for Adverse Effects grade 3 moist desquamation, other skin symptoms, and pain.Of 257 patients, 73 (28.4%) experienced extensive moist desquamation, 84 (32.7%) Common Terminology Criteria for Adverse Effects skin toxicity grade 3, and 57 (22.2%) a pain impacting on daily life activities. Among symptoms only grade 3 moist desquamation was significantly associated with severe pain (P.001). On multivariate analysis, smoking, high-energy photons, and skin bolus were significantly associated with severe moist desquamation. Skin toxicity doubled for smokers, with 40% severe pain, 48% grade 3 moist desquamation, and 64% grade 3 skin toxicity. Without skin bolus 4.2% had severe pain, none moist desquamation, and 2.1% grade 3 skin toxicity. When skin bolus was used on alternate days, the frequency increased to 15% for pain, 22% for moist desquamation, and 26% for grade 3 skin toxicity. When bolus was used daily, 32% had pain, 41% moist desquamation, and 47% grade 3 skin toxicity. Symptoms peaked 1 to 2 weeks after the end of PMRT.The present cohort study suggests excessive radiation toxicity after PMRT. Among factors associated with an increase of toxicity are smoking habits and the use of skin bolus.

Purpose Optimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM). Methods and Materials Women aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary outcomes of breast cancer–specific survival (BCSS), overall survival (OS) and secondary outcomes of local relapse–free survival (LRFS), locoregional relapse–free survival (LRRFS), and distant relapse–free survival (DRFS) were calculated using Kaplan-Meier methods and compared between BCT and MRM cohorts using log-rank tests. A planned subgroup analysis was performed on patients considered "ideal" for BCT (ie, T1N0, negative margins and no extensive ductal carcinoma in situ) and in whom local therapy may have the largest impact on survival because of low systemic risk. Results 965 patients were identified; 616 had BCT and 349 had MRM. The median follow-up time was 14.4 years (range, 8.4-23.3 years). Overall, 15-year rates of BCSS (76.0% vs 74.1%, P =.62), OS (74.2% vs 73.0%, P =.75), LRFS (85.4% vs 86.5%, P =.95), LRRFS (82.2% vs 81.6%, P =.61), and DRFS (74.4% vs 71.6%, P =.40) were similar between the BCT and MRM cohorts. In the "ideal" for BCT subgroup, there were 219 BCT and 67 MRM patients with a median follow-up time of 15.5 years. The 15-year BCSS (86.1% vs 82.9%, P =.57), OS (82.6% vs 82.9%, P =.89), LRFS (86.2% vs 84.2%, P =.50), LRRFS (83.1% vs 78.3%, P =.24), and DRFS (84.8% vs 79.1%, P =.17) were similar in the BCT and MRM cohorts. Conclusions This population-based analysis with long-term follow-up confirmed that women younger than 40 years treated with BCT had similar 15-year outcomes compared with MRM. Young age alone is not a contraindication to BCT.

Purpose To identify clinical and pathological factors that identify groups of women with stage I breast cancer with a 5-year risk of local recurrence (LR) ≤1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy (RT). Methods and Materials Study subjects were 5974 patients ≥50 years of age whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0 invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were examined using Kaplan-Meier methods. Recursive partitioning analysis was performed in patients treated with and without endocrine therapy to identify combinations of factors associated with a 5-year LR risk ≤1.5%. Results The median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to 91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10-year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine therapy, patient subsets identified with 5-year LR ≤1.5% included patients with grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus ≥60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively. Of 3144 patients treated without endocrine therapy, patients with grade 1 histology plus clear margins had 5-year LR ≤1.5% (n=821; LR, 0.6%; 95% CI, 0.1%-1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). Conclusions Histologic grade, age, margin status, and use of endocrine therapy identified 45% of a population-based cohort of female patients over age 50 with stage I breast cancer with a 5-year LR risk ≤1.5% after BCS plus RT. Prospective study is needed to evaluate the safety of omitting RT in patients with such a low risk of LR.

To evaluate whether local recurrence (LR) risk has changed over time among women with stage I breast cancer treated with breast-conserving therapy.Subjects were 5974 women aged ≥50 years diagnosis with pT1N0 breast cancer from 1989 to 2006, treated with breast-conserving surgery and radiation therapy. Clinicopathologic characteristics, treatment, and LR outcomes were compared among 4 cohorts stratified by year of diagnosis: 1989 to 1993 (n=1077), 1994 to 1998 (n=1633), 1999 to 2002 (n=1622), and 2003 to 2006 (n=1642). Multivariable analysis was performed, with year of diagnosis as a continuous variable.Median follow-up time was 8.6 years. Among patients diagnosed in 1989 to 1993, 1994 to 1998, 1999 to 2002, and 2003 to 2006, the proportions of grade 1 tumors increased (16% vs 29% vs 40% vs 39%, respectively, P.001). Surgical margin clearance rates increased from 82% to 93% to 95% and 88%, respectively (P.001). Over time, the proportions of unknown estrogen receptor (ER) status decreased (29% vs 10% vs 1.2% vs 0.5%, respectively, P.001), whereas ER-positive tumors increased (56% vs 77% vs 86% vs 86%, respectively, P.001). Hormone therapy use increased (23% vs 23% vs 62% vs 73%, respectively, P.001), and chemotherapy use increased (2% vs 5% vs 10% vs 13%, respectively, P.001). The 5-year cumulative incidence rates of LR over the 4 time periods were 2.8% vs 1.7% vs 0.9% vs 0.8%, respectively (Gray's test, P.001). On competing risk multivariable analysis, year of diagnosis was significantly associated with decreased LR (hazard ratio, 0.92 per year, P=.0003). Relative to grade 1 histology, grades 2, 3, and unknown were associated with increased LR. Hormone therapy use was associated with reduced LR.Significant changes in the multimodality management of stage I breast cancer have occurred over the past 2 decades. More favorable-risk tumors were diagnosed, and margin clearance and systemic therapy use increased. These changes contributed to the observed declining LR rates among patients treated with breast-conserving therapy.

Purpose To determine whether patients with Grade 3 early breast cancer have an inferior rate of local disease control at 10 years with hypofractionated radiotherapy compared with more conventionally fractionated schedules. Methods and Materials Local relapse rates were compared between patients receiving hypofractionated radiotherapy or conventionally fractionated radiotherapy to the whole breast in a population-based cohort of women with early-stage (T1-T2, N0, M0) Grade 3 breast cancers diagnosed between 1990 and 2000 and referred to the British Columbia Cancer Agency. Cumulative rates of local relapse were estimated using a competing risk method, and factors significant on univariate analysis were included with fractionation group in a multivariate model. The primary end point was local control at 10 years. Results A total of 1,335 patients with Grade 3 tumors were treated with adjuvant radiotherapy, 252 with conventional fractionation, and 1,083 with a hypofractionated schedule. The 10-year cumulative incidence of local relapse was 6.9% in the hypofractionated group and 6.2% in the conventionally fractionated group ( p = 0.99). Conclusions There is no evidence that hypofractionation is inferior to conventional fractionation for breast conserving therapy in patients with Grade 3 breast cancer in this large population-based series after 10 years of follow-up.

Purpose To report 3-year toxicity, cosmesis, and efficacy of a multicenter study of external beam, accelerated partial breast irradiation (APBI) for early-stage breast cancer. Methods and Materials Between March 2005 and August 2006, 127 women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study involving five Canadian cancer centers. Women meeting predefined dose constraints were treated with APBI using 3 to 5 photon beams, delivering 35 to 38.5 Gy in 10 fractions, twice a day, over 1 week. Patients were assessed for treatment-related toxicities, cosmesis, and efficacy before APBI and at specified time points for as long as 3 years after APBI. Results 104 women had planning computed tomography scans showing visible seromas, met dosimetric constraints, and were treated with APBI to doses of 35 Gy ( n = 9), 36 Gy ( n = 33), or 38.5 Gy ( n = 62). Eighty-seven patients were evaluated with minimum 3-year follow-up after APBI. Radiation dermatitis, breast edema, breast induration, and fatigue decreased from baseline levels or stabilized by the 3-year follow-up. Hypopigmentation, hyperpigmentation, breast pain, and telangiectasia slightly increased from baseline levels. Most toxicities at 3 years were Grade 1. Only 1 patient had a Grade 3 toxicity with telangiectasia in a skin fold inside the 95% isodose. Cosmesis was good to excellent in 86% (89/104) of women at baseline and 82% (70/85) at 3 years. The 3-year disease-free survival was 97%, with only one local recurrence that occurred in a different quadrant away from the treated site and two distant recurrences. Conclusions At 3 years, toxicity and cosmesis were acceptable, and local control and disease-free survival were excellent, supporting continued accrual to randomized APBI trials.

To compare the locoregional recurrence (LRR) rates in patients with nodal mirometastases (pNmic) with those in patients with node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; and to evaluate the LRR rates according to locoregional treatment of pNmic disease.The subjects were 9,616 women diagnosed between 1989 and 1999 with Stage pT1-T2, pN0, pNmic, or pNmac, M0 breast cancer. All women had undergone axillary dissection. The Kaplan-Meier local recurrence, regional recurrence, and LRR rates were compared among those with pN0 (n=7,977), pNmic (n=490) and pNmac (n=1,149) and according to locoregional treatment. Multivariate analysis was performed to identify the significant factors associated with LRR.The median follow-up was 11 years. The 10-year Kaplan-Meier recurrence rate in the pN0, pNmic, and pNmac cohorts was 6.1%, 6.8%, and 8.7% for local recurrence; 3.1%, 6.2%, and 10.3% for regional recurrence; and 8.0%, 11.6%, and 15.2% for LRR, respectively (all p.001). In the pNmic patients, the 10-year regional recurrence rate was 6.4% with breast-conserving surgery plus breast radiotherapy (RT), 5.4% with breast-conserving surgery plus locoregional RT, 4.6% with mastectomy alone, 11.1% with mastectomy plus chest wall RT, and 10.7% with mastectomy plus locoregional RT. In patients with pNmic disease and age45 years, Grade 3 histologic features, lymphovascular invasion, nodal ratio0.25, and estrogen receptor-negative disease, the 10-year LRR rates were 15-20%. On multivariate analysis of the entire cohort, pNmic was associated with greater LRR than Stage pN0 (hazard ratio [HR], 1.6; p=.002). On multivariate analysis of pNmic patients only, age45 years was associated with significantly greater LRR (HR, 1.9; p=.03), and trends for greater LRR were observed with a nodal ratio0.25 (HR, 2.0; p=.07) and lymphovascular invasion (HR, 1.7; p=.07).Women with pNmic had a greater risk of LRR than those with pN0 disease. Patients with pNmic in association with young age, Grade 3 histologic features, lymphovascular invasion, nodal ratio0.25, and estrogen receptor-negative disease experienced 10-year LRR rates of ∼15-20%, warranting consideration of locoregional RT.

(1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost.Subjects were 2,264 women with pT1-3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast ± boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer-specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed.Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with ≥4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, ≥4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p0.001).On univariable analysis, subsets with close or positive margins, in combination with age45 years, Grade III, LVI, and ≥4 positive nodes, have 5-year LR10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.

Purpose To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) ≤0.1 ng/ml vs those >0.1 ng/ml. Methods and Materials From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA ≤0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome. Results Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA ≤0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA ( p = 0.041), Gleason score ( p = 0.001), initial PSA ( p = 0.025), and T-stage ( p = 0.003), not ADT duration, as independent predictors of outcome. Conclusion Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities.

To examine variability in target volume delineation for partial breast radiotherapy planning and evaluate characteristics associated with low interobserver concordance.Thirty patients who underwent planning CT for adjuvant breast radiotherapy formed the study cohort. Using a standardized scale to score seroma clarity and consensus contouring guidelines, three radiation oncologists independently graded seroma clarity and delineated seroma volumes for each case. Seroma geometric center coordinates, maximum diameters in three axes, and volumes were recorded. Conformity index (CI), the ratio of overlapping volume and encompassing delineated volume, was calculated for each case. Cases with CI/=0.50 were analyzed to identify features associated with low concordance.The median time from surgery to CT was 42.5 days. For geometric center coordinates, variations from the mean were 0.5-1.1 mm and standard deviations (SDs) were 0.5-1.8 mm. For maximum seroma dimensions, variations from the mean and SDs were predominantly5 mm, with the largest SDs observed in the medial-lateral axis. The mean CI was 0.61 (range, 0.27-0.84). Five cases had CI/=0.50. Conformity index was significantly associated with seroma clarity (p0.001) and seroma volume (p0.002). Features associated with reduced concordance included tissue stranding from the surgical cavity, proximity to muscle, dense breast parenchyma, and benign calcifications that may be mistaken for surgical clips.Variability in seroma contouring occurred in three dimensions, with the largest variations in the medial-lateral axis. Awareness of clinical features associated with reduced concordance may be applied toward training staff and refining contouring guidelines for partial breast radiotherapy trials.

Purpose: To examine whether modified radical mastectomy (MRM) improves outcomes compared with breast-conserving treatment (BCT) in young women. Methods and Materials: Women aged 20–49 years, diagnosed with early breast cancer between 1989 and 1998, were identified. Management with BCT or MRM was compared for local (L), locoregional (LR), and distant relapse-free survival (DRFS) and breast cancer–specific survival (BCSS) by age group (20–39 years, 40–49 years). The analysis was repeated for patients considered “ideal” candidates for BCT: tumor size ≤2 cm, pathologically negative axillary nodes, negative margins, and no reported ductal carcinoma in situ. Results: A total of 1,597 women received BCT, and 801 had MRM. After a median follow-up of 9.0 years, the outcomes (L, LR, BCSS) were worse for the younger age group; however, the outcomes were not statistically different by type of local treatment. For women aged 20–39 years considered “ideal” for BCT, those treated with BCT had slightly lower LRFS compared with those treated with MRM (p = 0.3), but DRFS and BCSS were similar. Conclusions: A difference in LRFS at 10 years potentially favored MRM among women aged 20–39 years considered “ideal” BCT candidates but was not statistically significant and did not translate into a noticeable difference in DRFS or BCSS. Our data suggest that young age alone is not a contraindication to BCT.

Purpose: To identify patient subsets with T1-T2N0 breast cancer at high risk of locoregional recurrence (LRR) who may warrant consideration for postmastectomy radiotherapy. Methods and Materials: Data were analyzed for 1505 women referred between 1989 and 1999 with pathologic T1-T2N0M0 breast cancer treated with mastectomy with clear margins and no adjuvant radiotherapy. Logistic regression analysis was performed to identify statistically significant factors associated with LRR. Recursive partitioning was used to develop a classification tree model for LRR given the prognostic variables. Results: The median follow-up was 7.0 years. The 10-year Kaplan-Meier LRR rate was 7.8%. On logistic regression analysis, the statistically significant factors predicting LRR were histologic grade ( p p p = 0.05), and systemic therapy use ( p = 0.01). In the recursive partitioning model, the first split in the classification tree was histologic grade. For 972 patients without high-grade histologic features, the 10-year Kaplan-Meier LRR rate was 5.5%. For 533 patients with Grade 3 disease (LRR rate 12.1%), the concomitant presence of LVI was associated with a LRR rate of 21.2% ( n = 126). In patients with Grade 3 disease without LVI, T2 tumors conferred a LRR rate of 13.4% ( n = 194), which increased to 23.2% for patients who did not receive systemic therapy ( n = 63). Conclusion: Women with pT1-T2N0 breast cancer experienced a LRR risk of approximately 20% in the presence of Grade 3 disease with LVI or Grade 3 disease, T2 tumors, and no systemic therapy. These subsets of node-negative patients warrant consideration of for postmastectomy radiotherapy.

Objective Postoperative radiotherapy is frequently employed among breast cancer patients with positive surgical margins after mastectomy but there is little evidence to support this practice. This study examined relapse and survival among women with node-negative breast cancer and positive surgical margins after mastectomy. Methods Among 2570 women diagnosed between 1989 and 1998 and referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0 invasive breast cancer treated with mastectomy, 94 had positive surgical margins and formed the study cohort. Women with more established indications for postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease were excluded. Demographic, tumor, and treatment factors; relapse patterns; and Kaplan-Meier 8-year locoregional relapse-free, breast cancer–specific, and overall survival rates were compared between women who were treated with ( n = 41) and without ( n = 53) PMRT. Results Median follow-up time was 7.7 years. The distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen receptor status, and number of axillary nodes removed were similar between the two treatment groups. Six local chest wall recurrences (6.4%), 4 regional recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local relapse rates were 2.4% vs. 9.4% ( p = 0.23), and regional relapse rates were 2.4% vs. 5.7% ( p = 0.63), with and without PMRT, respectively. Trends for higher cumulative locoregional relapse (LRR) rates without PMRT were identified in the presence of age ≤50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%). Statistical significance was not demonstrated in these differences ( p > 0.10), possibly because of the small number of events. In patients with age >50 years, T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse occurred even with positive margins. PMRT did not improve distant relapse, 8-year breast cancer–specific and overall survival rates. Conclusion This study suggests that not all patients with node-negative breast cancer with positive margins after mastectomy require radiotherapy. Locoregional failure rates approximating 20% were observed in women with positive margins plus at least one of the following factors: age ≤50 years, T2 tumor size, grade III histology, or LVI. The absolute and relative improvements in locoregional control with radiotherapy in these situations support the judicious, but not routine, use of PMRT for positive margins after mastectomy in patients with node-negative breast cancer.

The effects of age and comorbidity on treatment and outcomes for patients with limited stage small-cell lung cancer (L-SCLC) are unclear. This study analyzes relapse and survival in a community-based population with L-SCLC according to age and comorbidity.A retrospective review was performed on 174 patients with L-SCLC referred to the British Columbia Cancer Agency, Vancouver Island Centre, between January 1991 and December 1999. Patient and treatment characteristics, disease response, relapse, and survival were compared among three age cohorts:65 years (n = 55, 32%), 65-74 years (n = 76, 44%), andor =75 years (n = 43, 25%); and according to Charlson comorbidity scores 0, 1, andor =2. Multivariate analysis was performed to identify independent prognostic factors associated with treatment response and survival.Patient factors that significantly differed with age were functional status classified by Eastern Cooperative Oncology Group performance status and number of comorbidities. Increasing age was significantly associated with fewer diagnostic scans. Combined modality chemoradiotherapy (CRT) was given in 86%, 66%, and 40% of patients ages65, 65-74, andor =75 years, respectively, (p0.0001). Thoracic irradiation use was comparable among the age cohorts (p0.05), but chemotherapy use varied significantly with less intensive regimens, fewer cycles, and lower total doses with advancing age (p0.05). Prophylactic cranial irradiation (PCI) was used in 41 patients, only 3 of whom were age70 years. Overall response rates to primary treatment significantly decreased with advancing age: 91%, 79%, and 74% in patients ages65, 65-74, andor =75 years, respectively (p = 0.014). Treatment toxicity and relapse patterns were similar across the age cohorts. Overall 2-year survival rates were significantly lower with advancing age: 37%, 22%, and 19% (p = 0.003), with corresponding median survivals of 17, 12, and 7 months among patients ages65, 65-74, andor =75 years, respectively. On multivariate analysis, age and Charlson comorbidity scores were not significantly associated with treatment response and survival. Independent prognostic factors favorably associated with survival were good performance status, normal lactate dehydrogenase, absence of pleural effusion, andor =four cycles of chemotherapy.Increasing age was associated with decreased performance status and increased comorbidity. Older patients with L-SCLC were less likely to be treated with CRT, intensive chemotherapy, and PCI. Treatment response and survival rates were lower with advancing age, but this may be attributed to poor performance status and suboptimal treatment rather than age.

To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial.Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only.Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients.In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.

To examine locoregional and distant recurrence (LRR and DR) in women with pT1-2N0 breast cancer according to approximated subtype and clinicopathologic characteristics.Two independent datasets were pooled and analyzed. The study participants were 1994 patients with pT1-2N0M0 breast cancer, treated with mastectomy without radiation therapy. The patients were classified into 1 of 5 subtypes: luminal A (ER+ or PR+/HER 2-/grade 1-2, n=1202); luminal B (ER+ or PR+/HER 2-/grade 3, n=294); luminal HER 2 (ER+ or PR+/HER 2+, n=221); HER 2 (ER-/PR-/HER 2+, n=105) and triple-negative breast cancer (TNBC) (ER-/PR-/HER 2-, n=172).The median follow-up time was 4.3 years. The 5-year Kaplan-Meier (KM) LRR were 1.8% in luminal A, 3.1% in luminal B, 1.7% in luminal HER 2, 1.9% in HER 2, and 1.9% in TNBC cohorts (P=.81). The 5-year KM DR was highest among women with TNBC: 1.8% in luminal A, 5.0% in luminal B, 2.4% in luminal HER 2, 1.1% in HER 2, and 9.6% in TNBC cohorts (P.001). Among 172 women with TNBC, the 5-year KM LRR were 1.3% with clear margins versus 12.5% with close or positive margins (P=.04). On multivariable analysis, factors that conferred higher LRR risk were tumors2 cm, lobular histology, and close/positive surgical margins.The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes. Among the subtypes, TNBC conferred the highest risk of DR and an elevated risk of LRR in the presence of positive or close margins. Our data suggest that although subtype alone cannot be used as the sole criterion to offer postmastectomy radiation therapy, it may reasonably be considered in conjunction with other clinicopathologic factors including tumor size, histology, and margin status. Larger cohorts and longer follow-up times are needed to define which women with node-negative disease have high postmastectomy LRR risks in contemporary practice.

To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer.Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examined outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics.Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts.Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal locoregional management for women with pN0(i+) breast cancer.

To determine the value of the intent to include internal mammary nodes (IMNs) in the radiation therapy (RT) volume for patients receiving adjuvant locoregional (breast or chest wall plus axillary and supraclavicular fossa) RT for breast cancer.2413 women with node-positive or T3/4N0 invasive breast cancer, treated with locoregional RT from 2001 to 2006, were identified in a prospectively maintained, population-based database. Intent to include IMNs in RT volume was determined through review of patient charts and RT plans. Distant relapse free survival (D-RFS), breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the two groups. Prespecified pN1 subgroup analyses were performed.The median follow-up time was 6.2 years. Forty-one percent of study participants received IMN RT. The 5-year D-RFS for IMN inclusion and exclusion groups were 82% vs. 82% (p = 0.82), BCSS was 87% vs. 87% (p = 0.81), and OS was 85% vs. 83% (p = 0.06). In the pN1 subgroup, D-RFS was 90% vs. 88% (p = 0.31), BCSS was 94% vs. 92% (p = 0.18), and OS was 91% vs. 88% (p = 0.01). After potential confounding variables were controlled for, women who received IMN RT did not have significantly different D-RFS (hazard ratio [HR] = 1.02 (95% confidence interval [CI], 0.84-1.24; p = 0.85), BCSS (HR = 0.98 (95% CI, 0.79-1.22; p = 0.88), or OS (HR = 0.95; 95% CI, 0.78-1.15; p = 0.57). In the pN1 subgroup, IMN RT was associated with trends for improved survival that were not statistically significant: D-RFS (HR = 0.87; 95% CI, 0.63-1.22; p = 0.42), BCSS (HR = 0.85; 95% CI, 0.57-1.25; p = 0.39), and OS (HR = 0.78; 95% CI, 0.56-1.09; p = 0.14).After a median follow-up time of 6.2 years, although intentional IMN RT was not associated with a significant improvement in survival, this population-based study suggests that IMN RT may contribute to improved outcomes in selected patients with N1 disease.

Purpose To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. Methods and Materials A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. Results Median follow-up time was 6.45 years (range, 0.09–15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level (≤0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS ( p = 0.033) and OS ( p = 0.018) rates, whereas age, T stage, Gleason score, and ADT duration (≤6 versus >6 months) were not predictive of outcomes. Conclusion In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.

Purpose Ipsilateral breast tumor recurrence (IBTR) can occur in 5–20% of women with early-stage breast cancer treated with breast-conserving therapy. Two entities of IBTR have been described: true recurrence (TR), suggested to be regrowth of disease at the tumor bed, and new primary (NP), distinct from the index lesion in histology and location. This study compared survival outcomes between two patient cohorts classified clinically as having either TR or NP. Methods and Materials Between 1989 and 1999, 6,020 women were referred to the BC Cancer Agency with newly diagnosed pT1–2, N0–1, M0 invasive breast cancer, treated with breast-conserving surgery. Of these, 289 patients had pathologically confirmed IBTR. Retrospective analysis was performed, and a set of decision rules was applied to classify cases as TR or NP based on change in histology, grade, hormone receptor status, and tumor location. Of 289 patients, 129 (45%) were classified as having TR and 139 (48%) as having NP; 21 (7%) were unclassified. Results The distributions of age at diagnosis, age at recurrence, and histopathologic factors were similar in the TR and NP cohorts (all p > 0.05). The mean time to recurrence was shorter in TR patients than in NP patients (4.8 years vs. 6.3 years, p = 0.001). Treatment of the IBTR did not differ between the two groups. In the TR and NP cohorts, breast cancer–specific survival was 55.7% vs. 61.3% ( p = 0.93), and overall survival was 43.7% vs. 54.8% ( p = 0.53). Conclusions Time to recurrence is significantly shorter in patients with IBTR classified as true recurrence compared to new primary. Non–statistically significant trends for less favorable survival were observed for patients with TR. Further investigation of the hypothesis that TR and NP tumors are distinct entities with different survival prognoses will require standardized pathology review and molecular analyses.

Purpose To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). Methods and Materials Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT ( n = 157), AccRT ( n = 57), or HypoRT ( n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. Results Median follow-up was 3.4 years. Three-year Kaplan–Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively ( p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS ( p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT ( p = 0.021). Kaplan–Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC ( p = 0.005) and OS ( p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use ( p p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. Conclusions In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.

Purpose The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for the rare presentation of pT3pN0cM0 breast cancer. The present analysis examined locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) in pT2 = 5.0-cm and pT3 >5.0-cm tumors treated with mastectomy, stratified by PMRT use. Materials and Methods Between January 1, 1989 and December 31, 2000, the British Columbia provincial database yielded 100 node-negative patients with tumors ≥5 cm of 19,846 nonmetastatic breast cancer patients (0.5%). Of these 100 patients, 44 (44%) had received adjuvant PMRT. Results The PMRT group contained significantly more pT3 >5-cm cases ( p = 0.001) and margin-positive cases ( p = .03). With a median follow-up of 10 years, the cumulative 10-year LRR rate was 2.3% (95% confidence interval, 0.2–10.5) in the PMRT group vs. 8.9% (95% confidence interval, 3.2–18.2) in the no-PMRT group ( p = .2). Regarding LRR in the no-PMRT group, all patients had Grade 3 histologic features (LRR 17%, 5 of 29) and had not received hormonal therapy (LRR 15%, 5 of 34). The 10-year breast cancer-specific survival rate was 85.8% (95% confidence interval 71.0–93.4) in the PMRT group vs. 74.6% (95% confidence interval 59.9–84.5) in the no-PMRT group ( p = .2). On multivariate analysis, adjusted for the prognostic and predictive variables, PMRT did not significantly improve the LRR or breast cancer-specific survival rates. Conclusion The present study demonstrated a low LRR rate for node-negative breast cancer ≥5 cm. Our results indicate that PMRT should be considered for Grade 3 histologic features and patients not undergoing hormonal therapy.

The role of three-dimensional breast ultrasound (3D US) in planning partial breast radiotherapy (PBRT) is unknown. This study evaluated the accuracy of coregistration of 3D US to planning computerized tomography (CT) images, the seroma contouring consistency of radiation oncologists using the two imaging modalities and the clinical situations in which US was associated with improved contouring consistency compared to CT.Twenty consecutive women with early-stage breast cancer were enrolled prospectively after breast-conserving surgery. Subjects underwent 3D US at CT simulation for adjuvant RT. Three radiation oncologists independently contoured the seroma on separate CT and 3D US image sets. Seroma clarity, seroma volumes, and interobserver contouring consistency were compared between the imaging modalities. Associations between clinical characteristics and seroma clarity were examined using Pearson correlation statistics.3D US and CT coregistration was accurate to within 2 mm or less in 19/20 (95%) cases. CT seroma clarity was reduced with dense breast parenchyma (p = 0.035), small seroma volume (p0.001), and small volume of excised breast tissue (p = 0.01). US seroma clarity was not affected by these factors (p = NS). US was associated with improved interobserver consistency compared with CT in 8/20 (40%) cases. Of these 8 cases, 7 had low CT seroma clarity scores and 4 had heterogeneously to extremely dense breast parenchyma.3D US can be a useful adjunct to CT in planning PBRT. Radiation oncologists were able to use US images to contour the seroma target, with improved interobserver consistency compared with CT in cases with dense breast parenchyma and poor CT seroma clarity.

Purpose To evaluate the effect of the time from surgery and other clinical factors on seroma volume and clarity and establish the optimal time to use the computed tomography (CT)-based seroma to plan partial breast irradiation (PBI). Methods and Materials A total of 205 women with early-stage breast cancer underwent planning CT after breast-conserving surgery. One radiation oncologist contoured the seroma volume and scored the seroma clarity, using a standardized Seroma Clarity Score scale, from 0 (not detectable) to 5 (clearest). Univariate and multivariate analyses were performed to evaluate the associations between the seroma characteristics and the interval from surgery and other clinical factors. Results The mean interval from surgery to CT was 84 days (standard deviation 59). During postoperative Weeks 3–8, the mean seroma volume decreased from 47 to 30 cm 3 , stabilized during Weeks 9–14 (mean 21) and was involuted beyond 14 weeks (mean 9 cm 3 ). The mean seroma clarity score was 3.4 at Weeks 3–8, 2.5 at Weeks 9–14, and 1.6 after 14 weeks. The seroma clarity was greater in patients aged ≥70 years. The seroma volume and clarity correlated significantly with the volume of excised breast tissue but not with the maximal tumor diameter, surgical re-excision, or chemotherapy use. Conclusion The optimal time to obtain the planning CT scan for PBI is within 8 weeks after surgery. During Weeks 9–14, the seroma might remain adequately defined in some patients; however, after 14 weeks, alternate strategies are needed to identify the PBI target. The lack of correlation between the seroma volume and tumor size suggests that the CT-based seroma should not be the sole guide for PBI target volume definition.

To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels20 ng/mL.A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD,12 months) or long term (LT-AD,or = 12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival. Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models.There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072).Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level20, irrespective of Gleason score or T stage.

To define the individual factors and combinations of factors associated with increased risk of locoregional recurrence (LRR) that may justify postmastectomy radiotherapy (PMRT) in patients with T1-T2 breast cancer and one to three positive nodes.The study cohort comprised 821 women referred to the British Columbia Cancer Agency between 1989 and 1997 with pathologic T1-T2 breast cancer and one to three positive nodes treated with mastectomy without adjuvant RT. The 10-year Kaplan-Meier estimates of isolated LRR and LRR with or without simultaneous distant recurrence (LRR +/- SDR) were analyzed according to age, histologic findings, tumor location, size, and grade, lymphovascular invasion status, estrogen receptor (ER) status, margin status, number of positive nodes, number of nodes removed, percentage of positive nodes, and systemic therapy use. Multivariate analyses were performed using Cox proportional hazards modeling. A risk classification model was developed using combinations of the statistically significant factors identified on multivariate analysis.The median follow-up was 7.7 years. Systemic therapy was used in 94% of patients. Overall, the 10-year Kaplan-Meier isolated LRR and LRR +/- SDR rate was 12.7% and 15.9%, respectively. Without PMRT, a 10-year LRR risk of20% was identified in women with one to three positive nodes plus at least one of the following factors: age45 years, Stage T2, histologic Grade 3, ER-negative disease, medial location, more than one positive node, or25% of nodes positive (all p0.05 on univariate analysis). On multivariate analysis, age45 years,25% of nodes positive, medial tumor location, and ER-negative status were statistically significant predictors of isolated LRR and LRR +/- SDR. In the classification model, the first split was according to age (45 years vs./=45 years), with 29.3% vs. 13.7% developing LRR +/- SDR (p0.0001). Of 123 women45 years, the presence of25% of nodes positive was associated with a risk of LRR +/- SDR of 58.0% compared with 23.8% for those with/=25% of nodes positive (p = 0.01). Of 698 women45 years, the presence of25% of nodes positive also conferred a greater LRR +/- SDR risk (26.7%) compared with women with/=25% of nodes positive (10.8%; p0.0001). In women45 years with/=25% of nodes positive, tumor location and ER status were factors that could be used to further distinguish low-risk from higher risk subsets.Clinical and pathologic factors can identify women with T1-T2 breast cancer and one to three positive nodes at high LRR risk after mastectomy. Age45 years,25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT.

To determine the role of endoscopic surveillance in predicting organ preservation and survival after primary chemoradiotherapy (CRT) for esophageal cancer.Fifty-six consecutive patients with nonmetastatic esophageal cancer were treated with primary CRT between May 1993 and April 1999 with curative intent and subsequent surveillance with endoscopy and CT scans. Patients with residual disease on endoscopy and/or CT 6 weeks after CRT were considered for immediate esophagectomy. The remaining patients continued endoscopic surveillance and were considered for esophagectomy only when local relapse was detected. Five-year survival was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed to identify significant factors associated with disease-specific survival.With a median follow-up of 62 months, the 5-year overall and disease-specific survival was 30% (95% confidence interval [CI]: 17%-43%) and 37% (95% CI: 22%-50%), respectively. Fourteen of 24 (58%) patients who survived more than 2 years did not require an esophagectomy. On univariate analysis, favorable prognostic factors for disease-specific survival were female gender (p = 0.026), CT-defined N(0) status (p = 0.027), and negative endoscopy at 6 weeks after CRT (p0.0001). On multivariate analysis, N(0) status and negative endoscopy after CRT remained significant (p = 0.03 and p0.0001, respectively) for disease-specific survival. On multivariate analysis for overall survival, female gender and negative endoscopy were significant (p = 0.35 and p0.001, respectively). The hazard ratios for disease-specific survival with positive nodal status and positive endoscopy were 2.44 (95% CI: 1.14-5.3) and 5.18 (95% CI: 2.3-11.6), respectively.Endoscopic response after primary CRT for esophageal cancer was the most significant predictive factor for overall and disease-specific survival. Regular endoscopic surveillance after CRT achieved survival rates comparable to other strategies and successfully preserved the esophagus in the majority of patients who survived more than 2 years.

The use of axillary dissection (AD) in women with invasive breast cancer is increasingly questioned. This study analyzes the survival in women with T1-2 breast cancer according to age and AD use.Data from the Breast Cancer Outcomes Unit Database were analyzed for 8038 women aged 50-89 years referred to the British Columbia Cancer Agency between 1989 and 1998 with invasive T1-2,M0 breast cancer. Tumor and treatment characteristics were compared between women treated with and without AD (AD+ vs. AD-) according to three age groups: 50-64, 65-74 and 75+ years. Regional relapse and actuarial 5-year overall and breast cancer-specific survival were compared between AD+ and AD- women. Multivariate analysis of age, tumor and treatment factors, and adjusted hazard ratios with AD omission were performed.AD was omitted more frequently with advancing age (4% vs. 8% vs. 22% in women aged 50-64, 65-74, and 75+ years, respectively, p0.0001). Tumor characteristics were more favorable in AD- women, with fewer having Grade III disease, T2 tumors, or lymphovascular invasion (all p0.0001). Women treated without AD were also less likely to undergo radiotherapy after lumpectomy or mastectomy (both p0.0001). Systemic therapy use and regional relapse rates were comparable between AD- and AD+ women in each age-specific cohort. Multivariate analysis identified age, tumor size, grade, lymphovascular invasion, estrogen receptor status, clinical nodal palpability, type of surgery, and radiotherapy use as independent variables affecting survival. Hazard ratios adjusted for these variables showed AD omission to be associated with lower overall survival in the entire cohort (hazard ratio 1.52, p0.0001) and lower breast cancer-specific survival in women aged 65-74 years (hazard ratio 1.99, p = 0.02).AD was more frequently omitted with advancing age. The lack of differences in systemic therapy use, regional relapse, and breast cancer-specific survival among AD- compared with AD+ women aged 75+ years suggests that AD use may be selectively omitted in this elderly cohort. However, the lower survival associated with AD omission among women aged 65-74 years, and the lack of a survival advantage among AD- women aged 50-64 years despite more favorable tumor characteristics and comparable systemic therapy use support the hypothesis that definitive locoregional therapy has an impact on survival.