Palliative radiotherapy utilization for cancer patients at end of life in British Columbia: retrospective cohort study.

BACKGROUND: The use of palliative radiotherapy (PRT) is variable in advanced cancer. Little is known about PRT utilization by end-of-life (EOL) cancer patients in Canada. This study examined the PRT utilization rates and factors associated with its use in a cohort of cancer patients who died in British Columbia (BC). METHODS: BC residents with invasive cancer who died between April 1, 2010 and March 31, 2011 were included in the study. Their cancer registry and radiotherapy treatment records were extracted from the BC Cancer Agency information systems and linked for the analysis. The PRT utilization rates by age, sex, primary cancer diagnosis, geographic region, survival time and travel time to the cancer centre were examined. Multivariable logistic regression was used to determine the factors that influenced the PRT utilization rates. RESULTS: Of the 12,300 decedents in the study 2,669 (21.7%) had received at least one course of PRT in their last year of life. The utilization rates dropped to 5.0% and 2.2% in the last 30 and 14 days of life, respectively. PRT utilization varied across diagnosis and was highest for lung cancer (45.7%) and lowest for colorectal cancer (8.9%). The rates also varied by age, survival time and travel time to the nearest radiotherapy centre. There was a greater odds of receiving PRT for those with primary lung cancer, survival time between 1.5-26 months from diagnosis or living within 2 hours from a cancer centre. The 85+ age group was least likely to receive PRT in their last year of life. CONCLUSIONS: This study found PRT utilization rates of EOL cancer decedents to be variable across the province of BC. Age, diagnosis, survival time and travel time to the nearest radiotherapy centre were found to influence the odds of PRT treatment. Further work is still needed to establish the appropriate PRT utilization rates for the EOL cancer population.

Predictors of local recurrence in a population-based cohort of women with ductal carcinoma in situ treated with breast conserving surgery alone.

BACKGROUND: To identify prognostic indicators of local recurrence (LR) in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conserving surgery (BCS) alone. METHODS: A retrospective study was conducted of all women with pure DCIS, diagnosed 1985-1999, referred for tertiary oncologic opinion in British Columbia, treated with BCS without adjuvant radiotherapy. Kaplan-Meier local control (LC) and breast cancer specific survival (BCSS) estimates for the entire group were plotted. Stratified analyses identified subgroups with high Kaplan-Meier 10-year LR. Cox multivariate modeling was used to assess predictors of LR. Kaplan-Meier BCSS rates were compared between two cohorts: those who experienced LR and those who did not have LR. RESULTS: A total of 460 women comprised the study cohort. Median follow-up was 9.4 years. The 15-year LC and BCSS rates were 82% and 97%, respectively. Stratified analyses of LR identified comedo histology, high nuclear grade, tumor size >4 cm or indeterminate size, and positive margins to be associated with significantly higher LR risk, with 10-year LR risks approximating 15-30%. The 10-year BCSS rates for the LR group were 94% compared with 99% for the NoLR group. On Cox regression modeling, high nuclear grade, the presence of comedocarcinoma, and positive margins were significant factors for higher risk of LR. CONCLUSIONS: Women with DCIS treated with BCS alone had higher LR risk, and those with a LR were more likely to die of breast cancer. Optimal local treatment is mandatory to minimize the risk of breast cancer death for women with this curable disease.

Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab.

BACKGROUND: We investigated the association of peripheral blood inflammatory markers with overall survival (OS) in pembrolizumab treated advanced non-small cell lung cancer (aNSCLC) patients with programmed death ligand 1 (PD-L1) expression ≥50%. Clinical risk factors for development of immune-related adverse events (irAE) were also explored. METHODS: aNSCLC patients with high PD-L1 expression receiving pembrolizumab monotherapy outside of clinical trials were identified retrospectively. All patients were treated at one of six British Columbia Cancer clinics between August 2017 and June 2019. Patients were dichotomized using baseline neutrophil-to-lymphocyte ratio (NLR,

Association of age with differences in immune related adverse events and survival of patients with advanced nonsmall cell lung cancer receiving pembrolizumab or nivolumab.

OBJECTIVES: To explore the association of age with development of immune related adverse events (irAE) and survival in patients with advanced nonsmall cell lung cancer (aNSCLC) receiving programmed cell death 1 antibodies (PD-1 Ab) outside of clinical trials. METHODS: A multicenter retrospective study of PD-1 Ab prescription for patients with aNSCLC between 06/2015-11/2018 at BC Cancer. Multivariable (MVA) logistic regression identified baseline variables associated with irAE manifested within 3 months of PD-1 Ab initiation. Overall survival (OS) analyzed in a propensity-score matched cohort and survival outcomes compared between age groups by stratified log-rank. Six-week landmark analysis was performed and OS compared between patients with interrupted versus continuous treatment by log-rank. RESULTS: Of 527 patients, 40.6% were age ≤ 64 years, 40.6% were 65-74 years, and 18.8% were ≥ 75 years. In MVA, ECOG performance status 2/3 (p = .034), squamous histology (p = .031), and nivolumab therapy (vs. pembrolizumab, p = .012) were associated with increased odds of irAE by 3 months of treatment. Across age groups no difference existed in any grade irAE (p = .98), hospitalization (p = 1.0), or corticosteroids use (p = .51). The propensity score-matched survival analysis comprised 77 patients from each age group; all covariates were balanced. OS did not differ significantly by age in the matched cohort (p = .17). Treatment interruption due to irAE at 6 weeks was more common in patient ≥75 years (vs. <75, p = .055) and correlated with lower OS (p = .002). CONCLUSION: In this cohort of patients with aNSCLC treated in routine clinical practice with PD-1 Ab, immune-toxicity and observed survival were similar amongst age groups.

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis.

INTRODUCTION: The programmed death 1 antibodies (PD-1 Ab) nivolumab and pembrolizumab improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). We evaluated the correlation between immune-related adverse events (irAE) and treatment interruption due to irAE on clinical efficacy of PD-1 Ab in advanced NSCLC. PATIENTS AND METHODS: Advanced NSCLC patients treated with PD-1 Ab between June 2015 to November 2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Common Terminology Criteria for Adverse Events, version 4.0) of irAE were abstracted from chart review. Kaplan-Meier curves of OS from initiation of PD-1 Ab were generated. Multivariable analysis with 6- and 12-week landmark analysis was performed by Cox proportional hazard regression models. RESULTS: In a cohort of 271 patients, irAEs were observed in 116 patients (42.8%). Nivolumab recipients developing colitis had lower OS compared to those who did not at the 6-week landmark (P = .010) and 12-week landmark (P = .072). For the entire cohort, 56 patients (20.7%) needed treatment interruption because of an irAE. Treatment interruption correlated with lower OS at the 6-week landmark (P = .005) and 12-week landmark (P = .008). Six-week landmark multivariable analysis identified Charlson Comorbidity Index score of 3 or higher, Eastern Cooperative Oncology Group Performance Status of 2 or higher, presence of liver metastases, and irAE greater than grade 2 versus no irAE to be associated with decreased OS (each P < .05). CONCLUSION: Treatment interruption due to irAE was associated with a lower median OS compared to continuous PD-1 Ab therapy. Shorter OS seen with severe irAE might reflect the need for improved physician education in irAE treatment algorithms.

Pembrolizumab for advanced nonsmall cell lung cancer: Efficacy and safety in everyday clinical practice.

OBJECTIVES: While pembrolizumab improves overall survival (OS) in a subset of advanced nonsmall cell lung cancer (aNSCLC) patients (pts) in clinical trials, individuals with poor Eastern Cooperative Oncology Group performance status (ECOG PS) were excluded. Furthermore, some studies have identified a potential link between improved pt outcomes and development of immune related adverse events (irAE.) In a large provincial cohort, we studied the efficacy and safety of pembrolizumab for poor ECOG PS pts and whether irAE correlate with improved OS. MATERIALS AND METHODS: aNSCLC pts treated with pembrolizumab between 06/2015 and 08/2018 at BC Cancer were retrospectively identified. Kaplan-Meier curves of OS from initiation of pembrolizumab were plotted. 3-, 6-, and 9- month landmark Kaplan-Meier analysis was performed and log-rank tests used to determine an association of irAE subtypes with OS. Multivariable logistic regression identified variables associated with grade ≥3 irAE within 3 months of pembrolizumab initiation. RESULTS: Of 190 pts, 74.2% were treatment naïve and 92.6% had PD-L1 expression ≥ 50%. Median OS in the 1st line and ≥2nd line settings were 24.3 months (95% CI, 9.7-not reached, NR) and 13.4 months (95% CI, 8.1-NR), respectively. Pts with ECOG PS 2/3 had lower median OS than if ECOG PS 0/1 (5.8 months vs. 16.7 months, p < 0.0001). In multivariable analysis, the odds of grade ≥ 3 irAE within 3 months was 6.3 fold higher if ECOG PS 2/3 versus 0/1 (p = 0.05). Development of pneumonitis at the 9 month landmark weakly correlated with decreased OS (p = 0.09). CONCLUSION: In the studied cohort, ECOG PS 2/3 pts had a significantly lower OS and greater odds of experiencing high-grade irAE than if ECOG PS 0/1. Development of irAE did not result in improved OS. Randomized trials to determine benefit of pembrolizumab for poor ECOG PS pts are needed.

Is multibeam IMRT better than standard treatment for patients with left-sided breast cancer?

PURPOSE: When treatment intent is to include breast and internal mammary lymph nodes (IMNs) in the clinical target volume (CTV), a significant volume of the heart may receive radiation, which may result in late morbidity. The value of conformal intensity-modulated radiation therapy (IMRT) to avoid heart dose was studied. METHODS AND MATERIALS: Breast, IMNs, and normal tissues were contoured for 30 consecutive patients previously treated with RT after lumpectomy for left-sided breast cancer. Eleven-beam, conformal, inverse-planned IMRT plans were developed and compared with best standard plans. Conformity Index (CI), Homogeneity Index (HI), and doses to normal tissues were compared. RESULTS: Intensity-modulated RT significantly improved (two-sided paired t test) HI (0.95 vs. 0.74), CI (0.91 vs. 0.48), volume of the heart receiving more than 30 Gy (V30-heart) (1.7% vs. 12.5%), and volume of lung receiving more than 20-Gy (V20-left lung) (17.1% vs. 26.6%), all p < 0.001. The mean Healthy Tissue Volume (HTV = CT set - PTV) dose was similar between IMRT and best standard plans (6.0 and 6.9 Gy, respectively), but IMRT increased the volume of normal tissues receiving low-dose RT: V5-right lung (13.7% vs. 2.0%), V5-right breast (29.2% vs. 7.9%), and V5-HTV (31.7% vs. 23.6%), all p < 0.001. IMRT plans were generated in less than 60 min and treatment delivered in approximately 20 min, suggesting that this technique is clinically applicable. CONCLUSIONS: IMRT significantly improved conformity and homogeneity for plans when the breast + IMNs were in the CTV. Heart and lung volume receiving high doses were decreased, but more healthy tissue received low doses. A simple algorithm based on amount of heart included in the standard plan showed limited ability to predict the benefit from IMRT.

Effect of Referral Patterns and Treatment Type on Oncologic Outcomes for Women with Ductal Carcinoma In Situ.

OBJECTIVE: Management of ductal carcinoma in situ (DCIS) remains controversial. This study examined long-term outcomes in a population-based cohort of patients with pure DCIS treated with breast-conserving surgery (BCS) alone, BCS + radiotherapy (RT), and mastectomy. Outcomes were compared between patients referred versus not referred for oncologic assessment after definitive surgery. MATERIALS AND METHODS: Subjects were 2575 women diagnosed between 1985 and 1999. Data from several electronic databases were linked and analyzed. Outcomes were invasive local recurrence-free survival (ILRFS), mastectomy-free survival (MFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: Median follow-up time was 9.8 years. Overall, 56% (n = 1448) of subjects were referred to a cancer centre. Factors associated with non-referral were older age, comorbidities, and travel distance. Ten-year MFS, BCSS, and OS were higher among referred patients (all p ≤ 0.001). In cohorts treated with BCS alone (n = 1314) vs. BCS + RT (n = 510) vs. mastectomy (n = 751), 10-year ILRFS were 93.7% vs. 96.6% vs. 97.7%, (p < 0.001) and BCSS were 97.6% vs. 99.8% vs. 98.6%, (p = 0.01). Corresponding rates of ipsilateral invasive breast relapse at 10 years were 6.3% after BCS alone, 3.4% after BCS + RT, and 2.3% after mastectomy (p < 0.001). On multivariable analysis, factors associated with improved ILRFS were older age at diagnosis, low comorbidity score, absence of comedo histology, mastectomy, and post-BCS RT. CONCLUSION: Patients with DCIS referred for oncologic assessment were more likely to undergo post-BCS RT, resulting in lower mastectomy and higher survival rates compared to non-referred patients. Patients with significant comorbidities were less likely to be referred and experienced lower ILRFS and BCSS. Referral for multidisciplinary oncologic assessment after surgery is warranted to individualize management and optimize outcomes for patients with DCIS.

Malignant Epithelial Transformation in Phyllodes Tumor: A Population-Based Case Series.

Background Phyllodes tumor (PT) of the breast is an uncommon fibroepithelial neoplasm. Malignant epithelial transformation in PT is rare. This study reports clinicopathologic characteristics and outcomes of patients with malignant epithelial transformation in PT. Methods From an institutional database of 183 patients with newly diagnosed PT referred to a Canadian provincial cancer institution between 1999 and 2014, 11 cases of PT with concomitant in situ or invasive carcinoma were identified. Descriptive analysis was performed to document the characteristics, treatment and outcomes of this cohort. Results Prevalence of malignant epithelial transformation in PT was 6.0%. Median (range) age was 54 (35-75) years. Types of carcinoma were ductal carcinoma in situ (DCIS) (n = 6), lobular carcinoma in situ (n = 4), and invasive ductal carcinoma (IDC) (n = 1). Median PT size was 5 (1-15) cm. Three PTs were classified as benign (27%), five as borderline (45%), and three as malignant (27%). Mastectomy was performed in six (55%) and breast conserving surgery in five (45%) patients. Hormonal therapy was used in two cases: one with a 1 cm, grade 2 DCIS, and one with an 11 cm, grade 1 IDC, the latter also receiving radiotherapy. Mean follow-up duration was 54 (6-175) months. None of the cases showed any evidence of disease after treatment at the time of their last follow-up. Conclusion This case series showed a higher prevalence of malignant epithelial transformation in PT than reported in previous literature. Outcomes were favourable despite the presence of either in situ or invasive carcinoma within PT.

Association of Radiotherapy Boost for Ductal Carcinoma In Situ With Local Control After Whole-Breast Radiotherapy.

IMPORTANCE: The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking. OBJECTIVE: To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; α = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015. INTERVENTIONS: Radiotherapy boost vs no boost. MAIN OUTCOMES AND MEASURES: Ipsilateral breast tumor recurrence. RESULTS: The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use. CONCLUSIONS AND RELEVANCE: This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.

Consistency in seroma contouring for partial breast radiotherapy: impact of guidelines.

PURPOSE: Inconsistencies in contouring target structures can undermine the precision of conformal radiation therapy (RT) planning and compromise the validity of clinical trial results. This study evaluated the impact of guidelines on consistency in target volume contouring for partial breast RT planning. METHODS AND MATERIALS: Guidelines for target volume definition for partial breast radiation therapy (PBRT) planning were developed by members of the steering committee for a pilot trial of PBRT using conformal external beam planning. In phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients was independently performed by a "trained" cohort of four radiation oncologists who were provided with these guidelines and an "untrained" cohort of four radiation oncologists who contoured without guidelines. Using automated planning software, the seroma target volume (STV) was expanded into a clinical target volume (CTV) and planning target volume (PTV) for each oncologist. Means and standard deviations were calculated, and two-tailed t tests were used to assess differences between the "trained" and "untrained" cohorts. In phase 2, all eight radiation oncologists were provided with the same contouring guidelines, and were asked to delineate the seroma in five new cases. Data were again analyzed to evaluate consistency between the two cohorts. RESULTS: The "untrained" cohort contoured larger seroma volumes and had larger CTVs and PTVs compared with the "trained" cohort in three of five cases. When seroma contouring was performed after review of contouring guidelines, the differences in the STVs, CTVs, and PTVs were no longer statistically significant. CONCLUSION: Guidelines can improve consistency among radiation oncologists performing target volume delineation for PBRT planning.

Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer.

BACKGROUND AND PURPOSE: Ongoing concern remains regarding cardiac injury with hypofractionated whole breast/chest-wall radiotherapy (HF-WBI) compared to conventional radiotherapy (CF-WBI) in left-sided breast cancer patients. The purpose was to determine if cardiac mortality increases with HF-WBI relative to CF-WBI. MATERIALS AND METHODS: Between 1990 and 1998, 5334 women with early-stage breast cancer received post-operative radiotherapy to the breast/chest wall alone. A population-based database recorded baseline patient, tumor and treatment factors. Baseline cardiovascular risk factors were identified from hospital administrative records. A propensity-score model balanced risk factors between radiotherapy groups. Cause of death was coded as breast cancer, cardiac or other cause. Cumulative mortality from each cause after radiotherapy was estimated using a competing risk approach. RESULTS: For left-sided cases, median follow-up was 14.2 years. 485 women received CF-WBI, 2221 women received HF-WBI. There was no difference in 15-year mortality from cardiac causes: 4.8% with HF-WBI and 4.2% with CF-WBI (p=0.74), even after propensity-score adjustment (p=0.45). There was no difference in breast cancer mortality or other cause mortality. For right-sided cases, there was no difference in mortality for the three causes of death. CONCLUSIONS: At 15-years follow-up, cardiac mortality is not statistically different among left-sided breast cancer patients treated with HF-WBI or CF-WBI.

A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer.

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.

Deformable versus rigid registration of PET/CT images for radiation treatment planning of head and neck and lung cancer patients: a retrospective dosimetric comparison.

BACKGROUND: The purpose of this study is to evaluate the clinical impact of using deformable registration in tumor volume definition between separately acquired PET/CT and planning CT images. METHODS: Ten lung and 10 head and neck cancer patients were retrospectively selected. PET/CT images were registered with planning CT scans using commercially available software. Radiation oncologists defined two sets of gross tumor volumes based on either rigidly or deformably registered PET/CT images, and properties of these volumes were then compared. RESULTS: The average displacement between rigid and deformable gross tumor volumes was 1.8 mm (0.7 mm) with a standard deviation of 1.0 mm (0.6 mm) for the head and neck (lung) cancer subjects. The Dice similarity coefficients ranged from 0.76-0.92 and 0.76-0.97 for the head and neck and lung subjects, respectively, indicating conformity. All gross tumor volumes received at least 95% of the prescribed dose to 99% of their volume. Differences in the mean radiation dose delivered to the gross tumor volumes were at most 2%. Differences in the fraction of the tumor volumes receiving 100% of the radiation dose were at most 5%. CONCLUSIONS: The study revealed limitations in the commercial software used to perform deformable registration. Unless significant anatomical differences between PET/CT and planning CT images are present, deformable registration was shown to be of marginal value when delineating gross tumor volumes.

Adjuvant hypofractionated versus conventional whole breast radiation therapy for early-stage breast cancer: long-term hospital-related morbidity from cardiac causes.

PURPOSE: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. METHODS AND MATERIALS: Between 1990 and 1998, 5334 women ≤ 80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. RESULTS: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). CONCLUSIONS: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.

Phase II study of accelerated hypofractionated three-dimensional conformal radiotherapy for stage T1-3 N0 M0 non-small cell lung cancer: NCIC CTG BR.25.

BACKGROUND: A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non-small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available. METHODS: Eighty patients with biopsy-proven, peripherally located, T1-3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions using a three-dimensional conformal technique without inhomogeneity correction. The gross tumour volume (GTV) was the primary tumor only, and the planning target volume (PTV) margin was 1.0 to 1.5cm. The primary endpoint was the 2-year primary tumor control rate. Toxicities were measured using the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: The median follow-up of patients was 49 months (range = 21-63 months). The median age of patients was 75.9 years. The actuarial rate of primary tumor control was 87.4% (95% confidence interval [CI] = 76.2% to 93.5%) at 2 years. Overall survival was 68.7% (95% CI = 57.2% to 77.6%) at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 8.8% (95% CI = 4.1% to 18.7%) and 21.6% (95% CI = 13.5% to 33.5%), respectively. Tumor size greater than 3cm was associated with an increased risk of developing distant relapse (hazard ratio = 3.11; 95% CI = 1.30 to 7.42; two-sided log-rank test P = .007). The most common grade 3+ toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10.0%) CONCLUSIONS: Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable primary tumor control and overall survival rates in patients with T1-3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple treatment technique.

Outcomes in patients treated with mastectomy for ductal carcinoma in situ.

PURPOSE: To examine, in a large, population-based cohort of women, the risk factors for recurrence after mastectomy for pure ductal carcinoma in situ (DCIS) and to identify which patients may benefit from postmastectomy radiation therapy. METHODS AND MATERIALS: Data were analyzed for 637 subjects with pure DCIS, diagnosed between January 1990 and December 1999, treated initially with mastectomy. Locoregional relapse (LRR), breast cancer-specific survival, and overall survival were described using the Kaplan-Meier method. Reported risk factors for LRR (age, margins, size, Van Nuys Prognostic Index, grade, necrosis, and histologic subtype) were analyzed by univariate (log-rank) and multivariate (Cox modeling) methods. RESULTS: Median follow-up was 12.0 years. Characteristics of the cohort were median age 55 years, 8.6% aged ≤ 40 years, 30.5% tumors >4 cm, 42.5% grade 3 histology, 37.7% multifocal disease, and 4.9% positive margins. At 10 years, LRR was 1.0%, breast cancer-specific survival was 98.0%, and overall survival was 90.3%. All recurrences (n=12) involved ipsilateral chest wall disease, with the majority being invasive disease (11 of 12). None of the 12 patients with recurrence died of breast cancer; all were successfully salvaged (median follow-up of 4.4 years). Ten-year LRR was higher with age ≤ 40 years (7.5% vs 1.5%; P=.003). CONCLUSION: Mastectomy provides excellent locoregional control for DCIS. Routine use of postmastectomy radiation therapy is not justified. Young age (≤40 years) predicts slightly higher LRR, but possibly owing to the small number of cases with multiple risk factors for relapse, a subgroup with a high risk of LRR (ie, approximately 15%) was not identified.

Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience.

PURPOSE: To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). METHODS AND MATERIALS: Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. RESULTS: Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age>60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). CONCLUSIONS: This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL-leg is a more aggressive disease; the excellent results in the rituximab group suggest it has an important role in management.

Treatment and outcomes of primary breast lymphoma.

PURPOSE: To evaluate treatment and outcomes in a population-based cohort of patients diagnosed with primary breast lymphoma. METHODS AND MATERIALS: Prognostic factors, management, and outcomes (local control, lymphoma-specific survival, and overall survival) were analyzed for all patients diagnosed with limited-stage, primary breast non-Hodgkin lymphoma (n = 50) diagnosed in British Columbia between 1981 and 2009. RESULTS: The median follow-up was 3.5 years; 64% presented with a breast mass. Histologic subtypes were indolent (n = 16 [32%]) or aggressive (n = 34 [68%]). Of those with indolent lymphoma, 81% had stage I, and 19% had stage II disease; 13% received no initial treatment; 75% received radiotherapy (RT) alone. One (6%) patient received surgical resection alone, and 1 (6%) patient received surgical resection in addition to RT. Of those with aggressive lymphoma, 62% had stage I and 38% had stage II disease; 3% received no initial treatment; 6%, RT alone; 38%, chemotherapy only; 41%, chemotherapy and RT; 9%, surgical resection alone; and 3%, surgical resection in addition to chemotherapy and RT. In patients with indolent and aggressive disease, 5-year local control estimates were 92% and 96%, lymphoma-specific survivals were 91% and 71%, and overall survivals were 75% and 54%, respectively. On univariate analysis, stage (I vs. II) (P = .006) and RT use (P = .032) were statistically significant predictors of improved overall survival in patients with indolent breast lymphoma. Combined chemoradiation was associated with a trend for improved overall survival (P = .061) in patients with aggressive disease. There were 4 cases of central nervous system relapse, all occurred in subjects with aggressive primary breast lymphoma. CONCLUSIONS: Patients with indolent breast lymphoma were most frequently treated with RT alone and achieved high rates of local control and survival. Patients with aggressive histology most often treated with chemotherapy, alone or combined with RT, had excellent local control but lower survival compared with indolent disease. Improved systemic therapies are needed to improve outcomes for patients with aggressive breast lymphoma.

Wait times in diagnostic evaluation and treatment for patients with stage III non-small cell lung cancer in British Columbia.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is associated with poor prognosis. Although this is mostly due to the aggressive natural history of the disease, the effect of treatment delays on patient outcomes is unclear. This study examines various time intervals in the diagnostic evaluation, staging, and treatment of patients with unresectable stage III NSCLC. METHODS: A case-control study of patients with stage III NSCLC in British Columbia was carried out. One hundred nineteen patients treated radically with chemoradiotherapy were matched with 238 patients treated palliatively. Multivariate analysis was used to compare treatment delays and prognostic factors in the 2 groups. RESULTS: Compared with radically treated cases, patients treated palliatively had shorter median times from first symptom to first abnormal test (32 vs. 58 d) and from first symptom to pathologically confirmed diagnosis (67 vs. 90 d). More radically treated patients (61% vs. 50%) were first assessed by a thoracic surgeon, whereas more palliatively treated patients (73% vs. 50%) were initially assessed by a respirologist. The median time from diagnosis to referral to a cancer center was similar between the 2 groups, but palliative cases were 5 times more likely to have a delay of >55 days between diagnosis and referral. This delay was observed in 24% of palliatively treated and 7% of radically treated cases. CONCLUSIONS: The wait time from first symptom to referral to a regional cancer center in British Columbia for stage III NSCLC was approximately 3 to 4 months. Efforts to reduce wait times are warranted to reduce patient distress and possibly disease progression.