The Influence of Histologic Grade on Outcomes of Elderly Women With Early Stage Breast Cancer Treated With Breast Conserving Surgery With or Without Radiotherapy

BackgroundTwo large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy.Materials and MethodsThe Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup.ResultsA total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043).ConclusionIn this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.     

Recommendations for Palliative and Hospice Care in NCCN Guidelines for Treatment of Cancer

BackgroundIntegration of specialist palliative care into routine oncologic care improves patients’ quality of life and survival. National Comprehensive Cancer Network (NCCN) cancer treatment guidelines are instrumental in standardizing cancer care, yet it is unclear how palliative and hospice care are integrated in these guidelines. In this study, we examined the frequency of occurrence of “palliative care” and “hospice care” in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines.Materials and MethodsWe reviewed all 53 updated NCCN Guidelines for Treatment of Cancer. We documented the frequency of occurrence of “palliative care” and “hospice care,” the definitions for these terms if available, and the recommended timing for these services.ResultsWe identified a total of 37 solid tumor and 16 hematologic malignancy guidelines. Palliative care was mentioned in 30 (57%) guidelines (24 solid tumor, 6 hematologic). Palliative care was mentioned more frequently in solid tumor than hematologic guidelines (median, 2 vs. 0; p = .04). Among the guidelines that included palliative care in the treatment recommendation, 25 (83%) only referred to NCCN palliative care guideline. Specialist palliative care referral was specifically mentioned in 5 of 30 (17%) guidelines. Only 14 of 24 (58%) solid tumor guidelines and 2 of 6 (33%) hematologic guidelines recommended palliative care in the front line setting for advanced malignancy. Few guidelines (n = 3/53, 6%) mentioned hospice care.Conclusion“Palliative care” was absent in almost half of NCCN cancer treatment guidelines and was rarely discussed in guidelines for hematologic malignancies. Our findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.Implications for PracticeIntegration of specialist palliative care into routine oncologic care is associated with improved patient outcomes. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have an important role to standardize palliative care involvement for cancer patients. It is unclear how often palliative care referral is recommended in these guidelines. In this study involving 53 NCCN Guidelines for Treatment of Cancer, the researchers found that palliative care was not mentioned in over 40% of NCCN guidelines and was rarely discussed in guidelines for hematologic malignancies. These findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.     

Quantifying the value of older adult-specific clinical trials: Post-lumpectomy irradiation among older adults with early-stage breast cancer

IntroductionAlthough there is increasing interest in conducting cancer clinical trials in older adults, the benefit of such trials is unclear. We aimed to quantify the real-world clinical and economic effects of two phase 3 trials (CALGB 9343 and PRIME II) which showed that post-lumpectomy radiation therapy (RT) improves loco-regional recurrence but makes no improvement in overall survival among older women with early-stage breast cancer (ESBC).Materials and MethodsWe developed a health-transition model to quantify the incremental clinical and economic outcomes between scenarios with vs. without older adult-specific trial results from a societal perspective between 2004 and 2018. The transition probabilities in the model were mainly derived from the 10-year results of CALGB 9343. The total number of the affected patient population in the US and the change in the probability of omitting post-lumpectomy RT due to the CALGB 9343 and PRIME II results were derived from a retrospective analysis of the SEER registry data for patients with ESBC. Sensitivity analyses were conducted to calculate the 95% credible interval (CR) of the incremental clinical and economic outcomes between the two scenarios.ResultsBetween 2004 and 2018, 32,936 (95% CR: 31,512, 34,357) fewer patients received post-lumpectomy RT among those aged 70 years or older diagnosed with ESBC in the US and there was a decrease cost of $419 M USD (95% CR: -$238 M, −$689 M) in scenarios with vs. without older adult-specific trial results. The difference in projected life years (1083 years, 95% CI: −2542, 7985) and QALYs (866 years, 95% CI: −2561, 7780) were not significant. At a willingness-to-pay threshold of $100 k/QALY, the probability of older adult-specific trial results generating a positive net monetary benefit was 98%.DiscussionThe CALGB 9343 and PRIME II trial results were associated with a substantial cost-saving in the US society. Our results suggest that older adult-specific clinical trials that demonstrate no survival benefit of an intervention in older adults could be correlated with a significant monetary benefit. Further case studies are needed for different types of older adult-specific trials to understand the value of older adult-specific trials comprehensively.     

Omission of radiation therapy after breast-conserving surgery in the United States: a population-based analysis of clinicopathologic factors

BACKGROUND:

Radiation therapy (RT) after breast‐conserving surgery (BCS) is associated with a significant reduction in ipsilateral breast tumor recurrence and breast cancer mortality rates in patients with early stage breast cancer. The authors of this report sought to determine which patients with breast cancer do not receive RT after BCS in the United States.

METHODS:

The Surveillance, Epidemiology, and End Results registry was used to determine the rates of RT after BCS for women with stage I through III breast cancer in the United States from 1992 through 2007. A multivariate analysis was performed to identify independent predictors of omission of RT.

RESULTS:

In total, 294,254 patients with invasive, nonmetastatic breast cancer were identified who underwent surgery from 1992 through 2007. Most patients (57%) underwent BCS; among those, 21.1% did not receive RT after BCS. The omission of RT increased significantly from 1992 (15.5%) to 2007 (25%). The receipt of RT also decreased significantly for patients with increased cancer stage, age <55 years, high‐grade tumors, large tumors, positive or untested lymph node status, African American or Hispanic race, and negative or unknown estrogen receptor status. Significant geographic variation was observed in the rates of RT after BCS.

CONCLUSIONS:

The omission of RT after BCS was more common in recent years, especially among women who had an increased risk of breast cancer recurrence. This trend represents a serious health care concern because of the potential increased risk of local recurrence and breast cancer mortality. Cancer 2012. © 2011 American Cancer Society.     

Health Care Disparities and Demand for Expanding Hereditary Breast Cancer Screening Guidelines in African Americans

BackgroundGenomic medicine has led to significant advancements in the prevention and treatment of cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommend BRCA1/2 screening in high-risk individuals; however, the guidelines have not incorporated differences within ethnic cohorts beyond Ashkenazi Jewish ethnicity. We analyzed the prevalence of BRCA1/2 mutations in various ethnicities and identified high-risk personal characteristics and family history incorporating differences within ethnic cohorts beyond Ashkenazi Jewish ethnicity.Patients and MethodsWe reviewed data collected by a Michigan medical genetic clinic in a community-based hospital from 2008 to 2018. A retrospective chart analysis was conducted of 1090 patients who received genetic counseling regarding hereditary cancer syndromes.ResultsWe found a statistically significant higher rate of pathogenic BRCA1/2 mutation prevalence in African American patients, at 8.1%, compared to non-Ashkenazi Jewish white patients, at 3.6% (P = .02). African Americans have a mutational prevalence nearing that of the Ashkenazi Jewish population.ConclusionRevision of the NCCN guidelines regarding hereditary cancer syndrome testing in various ethnic groups is imperative and overdue. Future studies are needed to identify health care disparities in and socioeconomic barriers to genetic testing.     

Omission of radiotherapy in elderly patients with early breast cancer: 15-Year results of a prospective non-randomised trial

BackgroundWhether radiotherapy (RT) is beneficial in elderly (⩾70 years) patients undergoing conservative surgery for early breast cancer has long been controversial. Recent randomised trials show that most elderly patients do not benefit from RT. We started a prospective non-randomised trial to address this issue in 1987 and now present results for the 627 consecutive pT1/2cN0 patients recruited, and treated by conservative surgery (quadrantectomy) and tamoxifen, and assigned non-randomly to RT or no RT.MethodsWe used multivariate competing risks models to estimate 15-crude cumulative incidence (CCI) of ipsilateral breast tumour recurrence (IBTR), distant metastasis and breast cancer mortality. The models incorporated a propensity score as a measure of probability of receiving RT based on baseline characteristics, to account for the lack of randomisation.ResultsFor pT1 patients, 15-year CCIs of IBTR, distant metastasis and breast cancer death were indistinguishable in the RT and no RT groups. For pT2 patients, 15-year CCI of IBTR was much higher in those not given RT (14.6% versus 0.8%, p = 0.004), although breast cancer mortality and distant metastasis did not differ significantly between RT and no RT.ConclusionsConsistent with the findings of recent randomised trials, our long-term data indicate that most elderly, ER-positive patients with pT1 cN0 breast cancer treated by quadrantectomy do not benefit from RT. The 14.6% CCI of IBTR in our pT2 patients is an additional finding not presented in the trials and suggests that RT should be administered to elderly patients with pT2 disease.     

Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840

BackgroundTwo Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer.Patients and methodsCALGB 9840 evaluated weekly paclitaxel (80 mg/m²) versus paclitaxel every 3 weeks (175 mg/m²); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m² each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55–64 years (29%), and (iii) ≥65 years (26%).ResultsTumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade ≥3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity.ConclusionsOlder women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects.     

Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis

BackgroundData guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment.Materials and MethodsThere were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS).ResultsMedian follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes.ConclusionIn this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.     

Regional Nodal Irradiation for Clinically Node-Positive Breast Cancer Patients With Pathologic Negative Nodes After Neoadjuvant Chemotherapy

IntroductionNeoadjuvant chemotherapy (NAC) is increasingly used for operable breast cancer (BC). Appropriate radiation therapy (RT) fields (ie, whole breast [WB] ± regional nodal irradiation [RNI]) in patients who were clinically node positive (cN1) but convert to pathologically node negative (ypN0) after NAC are unknown and the subject of the accruing NSABP B-51 trial. We sought to compare outcomes between WB RT with or without RNI following breast conservation and sentinel lymph node biopsy (SLNB) alone in cN1, ypN0 women following NAC.Patients and MethodsWe identified all BC patients with cN1, ypN0 who underwent NAC followed by lumpectomy and SLNB between 2006 and 2015 in the National Cancer Database. RNI utilization was evaluated using Cochran-Armitage test. Overall survival between WB RT alone versus WB + RNI was compared using Kaplan-Meier with and without propensity score-based weighted adjustment and multivariable (MVA) Cox proportional hazards.ResultsFrom 2006 to 2015, RNI use increased from 48.13% to 62.13% (Pfor trend <.001). The 10-year survival for WB alone versus WB + RNI was 83.6% and 79.5%, respectively (P= .14). On MVA analysis, the addition of RNI compared to WB alone was not associated with a survival benefit (WB vs. WB + RNI: hazard ratio 0.80, 95% confidence interval, 0.58-1.11, P= .19). Results were unchanged after propensity score-based adjustment.ConclusionFor women with cN1 BC who convert to ypN0 following NAC and breast conserving surgery with SLNB alone, more extensive RNI may not provide a long-term survival benefit. Prospective validation via the NSABP B-51 trial will be essential.     

La radiothérapie mammaire hypofractionnée en 13 séances,parfaite tolérance ou réaction cutanée décalée ? Étude prospective de l’institut Curie

PurposeTo assess the skin toxicity of this scheme and the time to its appearance.Patients and methodsEighty-one prospectively recorded patients (pts), treated in Radiotherapy Department for Breast Cancer (BC) with radiotherapy (RT) to the whole breast at the dose of 42.9 Gy per 13 fractions (F) per 5 weeks have been studied. Skin reactions were monitored weekly using the National Cancer Institute-Common Toxicity Criteria scoring system, version 3. All risk factors as tobacco smoking, diabetes, obesity were also recorded.ResultsAll 81 pts, aged from 40 to 83 years (median: 70 years) received whole breast RT 42.9 Gy per 13 F without lymph node irradiation after breast conserving surgery. There were no pts with concurrent chemo- and/or hormonal therapy. Seventeen patients (21%) have been treated using decubitus dorsal (DD) technique and 64 (79%) using the previously described isocentric decubitus lateral (IDL) technique. During the RT, only 34 pts (42%) experienced grade I skin reactions and 47 pts (58%) were without. At the last day of the breast irradiation, there were 66 (81%) grade I (N = 59) and II (N = 7) skin reactions and 15 pts (19%) without. The early skin tolerance of this scheme was considered to be excellent. But in the 2 weeks after the RT, 20 pts (25%) asked for new clinics with their radiation oncologist as a matter of urgency due to worsening of their skin condition. All of them have been seen by their physician and/or the nurse. Of them, nine presented grade I and 11 presented grade II skin reactions, with necessity of special skin care. The analysis of these results was realized and delayed clinics were organized for all pts treated with this scheme 10–14 days after the end of the radiation treatment.ConclusionsThe breast RT 42.9 Gy/13 F have been previously described as an efficacious and well tolerated scheme. This prospective homogeneous group of patients showed that delayed early skin reactions could appear in some cases. Therefore complementary clinics are needed to detect and treat these reactions.     

Predictors of Whole Breast Radiation Therapy Completion in Early Stage Breast Cancer Following Lumpectomy

BackgroundWhole breast radiation therapy (RT) has become standard of care in early stage breast cancer treatment following lumpectomy. Predictors of RT completion have been sparsely studied, with no previous nationwide examination of the impact of fractionation regimen on completion rate.Patients and MethodsThe National Cancer Database identified patients with early stage breast cancer having undergone lumpectomy and RT from 2004 through 2015. Fraction size of 1.8-2.0 Gray (Gy) was defined as standard fractionation (SFRT); 2.66-2.70 Gy/fraction as hypofractionation (HFRT). RT completion was defined as receipt of at least 46 Gy for SFRT and 40 Gy for HFRT. A multivariable logistic regression model characterized RT completion predictors.ResultsA total of 100,734 patients were identified where fraction size could be reliably characterized as above; more than 87% completed RT. Of these, 66.8% received SFRT, yet HFRT use significantly increased over time (5.2% increase/year; P < .0001). RT completion rates were significantly greater following HFRT (99.3%) versus SFRT (79.7%); patients receiving SFRT had higher odds of not completing RT (odds ratio, 41.5; 95% confidence interval, 36.6-47.1; P < .0001). Multivariable analysis revealed that African-American and Caucasian patients treated with SFRT versus HFRT had 22 and 43 times the odds of not completing RT, respectively (P < .0001).ConclusionsSFRT remained the majority of RT fractionation in the studied time period, although HFRT use has increased over time. Patients residing > 10 miles from a treatment facility or of African-American race had lower odds of completing RT, as were patients treated with SFRT versus HFRT. These findings suggest compliance advantages of HFRT for patients with early stage breast cancer having undergone lumpectomy.     

The Impact of Locoregional Treatment on Survival in Patients With Metastatic Breast Cancer: A National Cancer Database Analysis

BackgroundAlthough systemic therapy is the standard treatment for metastatic breast cancer, the value of locoregional treatment (LRT) of the primary tumor and its impact on survival is controversial. This study evaluates survival outcomes in patients with metastatic breast cancer after receiving LRT (surgery and/or radiation therapy) of the primary tumor.Materials and MethodsThe National Cancer Database was used to identify 16,128 qualifying cases of metastatic breast cancer who received systemic therapy with or without LRT from 2004 to 2013. Treatment modality was divided into surgery (Sx), radiation therapy (RT), surgery followed by RT (Sx + RT), and no LRT. The median survival and 3-year actuarial survival rates (OS) were analyzed for each treatment group. On multivariate analyses, adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using Cox regression modeling to adjust for patient and clinicopathologic characteristics.ResultsOverall, the median follow-up was 28.3 months, and the median survival for all patients was 37.2 months. With 9761 deaths reported, the estimated 3-year OS was 51.3%. The Sx + RT group (n = 2166) had the highest 3-year OS of 69.4%, followed by the Sx group (n = 4293) with 57.6%, the no LRT group (n = 8955) with 44.3%, and the RT group (n = 714) with 41.5% (P < .0001). On multivariate analysis, compared with the no LRT group, a decreased HR was noted in patients receiving Sx (adjusted HR, 0.68; 95% CI, 0.65-0.71; P < .0001) and Sx + RT (adjusted HR, 0.46; 95% CI, 0.43-0.49; P < .0001).ConclusionLRT, especially surgery followed by RT, in addition to systemic therapy, was associated with improved survival in patients with metastatic breast cancer.     

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction.     

Cyclin-Dependent Kinase 4/6 Inhibitors Combined With Radiotherapy for Patients With Metastatic Breast Cancer

BackgroundThe cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard treatment for hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. Data about the balance between efficacy and toxicity of combined palliative radiotherapy (RT) and CDK4/6 inhibition are lacking.Patients and MethodsWe undertook a review of 46 patients with metastatic breast cancer on systemic treatment with CDK4/6i who underwent 62 metastases-directed RT. Clinical, laboratory, and RT treatment planning data were collected. Statistical analyses included Student t test, paired sample t test, and logistic regression modeling.ResultsThirty patients (65.2%) received palbociclib, 15 (32.6%) received ribociclib, and one patient received abemaciclib (2.2%). Median total prescribed RT dose was 20 Gy (range, 8-63 Gy). Sites of RT were bone (n = 50; 80.7%), visceral (n = 7; 11.3%), or brain metastases (n = 3; 4.8%), as well as primary tumor of the breast (n = 2; 3.2%). Overall, the rates of grade 3 or higher adverse events (AEs) were 6.5%, 4.3%, 15.2%, and 23.9% before the start of RT, during RT, 2 and 6 weeks after RT completion, respectively. We found no correlation between dose distribution to organs at risk and the development of AEs. The local control rates for the entire cohort were 98% at 6 months and 90% at 12 months. Overall, pain relief (complete or partial) was experienced by 80% (24/30) of patients who initially reported pain at the treated metastatic site.ConclusionWe observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT.     

The Role of Radiation in All Stages of Nodular Lymphocytic Predominant Hodgkin Lymphoma

BackgroundThe goal of this study was to assess the survival differences seen in early-stage and advanced-stage nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) based on treatment modality.Patients and MethodsThe National Cancer Database was queried to identify patients diagnosed with NLPHL between 2004 and 2012. Overall survival (OS) was determined using univariate and multivariate Cox regression analysis. Kaplan-Meier and log-rank analysis were used to estimate differences in OS between treatment groups.ResultsA total of 1968 patients were identified for analysis, consisting of stage I (40.4%), stage II (29.3%), stage III (22.3%), and stage IV (8.0%) disease. The median age of patients was 46 years. The following factors were predictive of radiotherapy (RT) omission in treatment: increasing age, black race, Medicare insurance, chemotherapy use, stage II to IV disease, and the presence of B-symptoms. On survival analysis, RT was associated with prolonged OS in all stages of NLPHL (50.1 vs. 42.4 months; P < .01). The OS benefit of RT persisted on multivariate analysis (hazard ratio, 0.37; P < .01). On subset analysis, RT was associated with prolonged OS in early disease (49.8 vs. 45.5 months; P < .01), whereas a trend towards an OS benefit was observed in advanced-stage (54.1 vs. 39.6 months; P = .06) NLPHL. Radiotherapy was also associated with prolonged OS among patients with B-symptoms (49.0 vs. 42.6 months; P < .01).ConclusionThe use of RT in NLPHL is less likely among those with advanced-stage disease and B-symptoms. However, we found RT to be associated with prolonged OS in all stages of NLPHL, including those with B-symptoms.     

De-escalating Locoregional Therapy for Axillary Micrometastases in Breast Cancer: How Much is Too Much?

BackgroundThe applicability of modern prospective data on adjuvant radiotherapy (RT) fields in patients with micrometastases is limited because many trials occurred prior to routine measurement of nodal metastasis size and modern sentinel lymph node evaluation techniques. We aimed to determine prognostic factors for patients with micrometastases and evaluate the impact of adjuvant RT on disease outcomes.Patients and MethodsPatients diagnosed with pathologic T1-T3 N1mi breast cancers between 2004-2015 were identified. Cox proportional hazards methods were used to determine characteristics predictive of locoregional recurrence (LRR). Tumor and treatment-specific factors were further evaluated using log-rank statistics to compare rates of LRR-free survival.ResultsThis analysis included 156 patients. On multivariable analysis, grade 3 histology (HR 10.84, 95% CI 2.72-43.21) and adjuvant RT (HR 0.22, 95% CI 0.06-0.81) were independent predictors of LRR. Among patients with grade 1-2 histology, 5-year LRR-free survival was 98.8% in patients who received adjuvant RT versus 100% in patients who did not receive adjuvant RT (P = .82). Among patients with grade 3 histology, 5-year LRR-free survival was 90.1% in patients who received adjuvant RT versus 53.0% in patients who did not receive adjuvant RT (P = .025), and 100% in patients receiving comprehensive nodal irradiation versus 76.7% in patients receiving whole breast irradiation or no RT (P = .045).ConclusionPatients with grade 3 micrometastases are at substantial risk for LRR. Adjuvant RT, including comprehensive nodal irradiation, should be strongly considered in these women.     

T1-2N0M0 Triple-Negative Breast Cancer Treated With Breast-Conserving Therapy Has Better Survival Compared to Mastectomy: A SEER Population-Based Retrospective Analysis

BackgroundFor early-stage breast cancer, the two current mainstay treatments are breast-conserving therapy (BCT; lumpectomy followed by radiotherapy [RT] and BCT) and mastectomy. Generally, triple-negative breast cancer (TNBC) is more aggressive compared to hormone receptor–positive breast cancer. We sought to investigate the effect of BCT compared to mastectomy on overall survival (OS) and breast cancer–specific survival (BCSS) in T1-2N0M0 TNBC.Patients and MethodsA population-based retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Patients included in the analysis were divided into 3 groups according to surgical modality and RT: BCT, mastectomy alone, and mastectomy with RT. The survival end points were OS and BCSS, and survival analysis was performed by the Kaplan-Meier method and the log-rank test among treatment types.ResultsA total of 14,910 female subjects with T1-2N0M0 TNBC diagnosed between 2010 and 2014 were included. A total of 7381 patients had BCT; 6967 had mastectomy alone, and 562 had mastectomy with RT. Patients treated with BCT had better OS (log-rank P < .05) and BCSS (log-rank P < .05) than those receiving mastectomy with or without RT. The 5-year OS was 88.6% for BCT, 83.0% for mastectomy alone, and 79.6% for mastectomy with RT. The 5-year BCSS was 94.3% for BCT, 93.3% for mastectomy alone, and 83.7% for mastectomy with RT.ConclusionIn patients with T1-2N0M0 TNBC, BCT was associated with superior OS and BCSS compared to mastectomy with or without RT. After mastectomy, there was no evidence of survival benefit of RT.     

Assessment of the external validity of the National Comprehensive Cancer Network (NCCN) guidelines for pancreatic ductal adenocarcinoma in a population of older patients aged 70 years and older

IntroductionPancreatic ductal adenocarcinoma (PDAC) mainly occurs in older adults. Since randomized clinical trials (RCTs) provide the highest-quality evidence incorporated in NCCN recommendations, the underrepresentation of older patients in RCTs challenges guidelines' external validity and limits the solidity of evidence in this specific population.Materials and MethodsThe study aimed to investigate external validity of NCCN guidelines for PDCA and the impact of reference studies eligibility on overall survival (OS) in a real-world older population. We retrieved RCTs supporting NCCN recommendations for management of PDAC and identified ten topics. We matched a cohort of 707 PDAC patients aged ≥70 years from the Moffitt Cancer Center database with eligibility criteria of 96 reference RCTs to check the proportion of patients eligible for at least two RCTs. Eligibility >60% was rated full validity, 30%–60% partial validity and < 30% limited validity. We also performed log-rank test to assessed whether “eligibility” status affects OS, stratifying by age (70–74; 75–79; ≥80).Results and DiscussionWe found full validity for neoadjuvant (57/73 patients; 69.86%), locally advanced (28/39; 71.79%) and second line (88/110; 80%) treatment, while lowest validity was found for adjuvant chemotherapy (37/86; 43%). Eligible status was correlated with a significant OS benefit for adjuvant chemoradiation (p = 0.002) in all-comers and for first-line polychemotherapy in patients aged ≥80 (p = 0.01).Our analysis supports the limitation of guidelines' external validity in older patients, and hints at possible correlations with survival, although no definitive conclusions can be drawn at this stage. Renewing RCT design with broader eligibility criteria might help increase inclusion of older and thus strengthen the evidence.     

Incidence and Onset of Severe Cardiac Events After Radiotherapy for Esophageal Cancer

IntroductionLate cardiotoxicity related to radiotherapy (RT) in breast cancer and Hodgkin’s lymphoma has been well-reported. However, the relatively higher cardiac dose exposure for esophageal cancer (EC) may result in the earlier onset of cardiac diseases. In this report, we examined the incidence, onset, and long-term survival outcomes of high-grade cardiac events after RT in a large cohort of patients with EC.MethodsBetween March 2005 and August 2017, a total of 479 patients with EC from a prospectively maintained institutional database at The University of Texas MD Anderson Cancer Center were analyzed. All patients were treated with either intensity-modulated RT or proton beam therapy, either preoperatively or definitively. We focused on any grade 3 or higher (G3+) cardiac events according to the Common Terminology Criteria for Adverse Events, version 5.0.ResultsG3+ cardiac events occurred in 18% of patients at a median of 7 months with a median follow-up time of 76 months. Preexisting cardiac disease (p = 0.001) and radiation modality (intensity-modulated RT versus proton beam therapy) (p = 0.027) were significantly associated with G3+ cardiac events. Under multivariable analysis, the mean heart dose, particularly of less than 15 Gy, was associated with reduced G3+ events. Furthermore, G3+ cardiac events were associated with worse overall survival (p = 0.041).ConclusionsSevere cardiac events were relatively common in patients with early onset EC after RT, especially those with preexisting cardiac disease and higher radiation doses to the heart. Optimal treatment approaches should be taken to reduce cumulative doses to the heart, especially for patients with preexisting cardiac disease.     

No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial,SweBCG 91 RT

BackgroundBreast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients.Patients and methodsA total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program.ResultsAfter 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P < 0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P = 0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P = 0.68, nor was breast cancer–specific mortality significantly higher.ConclusionsRT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.