Identifying factors that impact survival among women with inflammatory breast cancer

BackgroundThe objective of this retrospective study was to determine factors impacting survival among women with inflammatory breast cancer (IBC).MethodsThe Surveillance, Epidemiology and End Results Registry (SEER) was searched to identify women with stage III/IV IBC diagnosed between 2004 and 2007. IBC was identified within SEER as T4d disease as defined by the sixth edition of the American Joint Committee on Cancer. The Kaplan–Meier product-limit method was used to describe inflammatory breast cancer-specific survival (IBCS). Cox models were fitted to assess the multivariable relationship of various patient and tumor characteristics and IBCS.ResultsTwo thousand three hundred and eighty-four women with stage IIIB/C and IV IBC were identified. Two-year IBCS among women with stage IIIB, IIIC and IV disease was 81%, 67% and 42%, respectively (P < 0.0001). In the multivariable model, patients with stage IIIB disease and those with stage IIIC disease had a 63% [hazard ratio (HR) 0.373, 95% confidence interval (CI) 0.296–0.470, P < 0.001] and 31% (HR 0.691, 95% CI 0.512–0.933, P = 0.016) decreased risk of death from IBC, respectively, compared with women with stage IV disease. Other factors significantly associated with decreased risk of death from IBC included low-grade tumors, being of white/other race, undergoing surgery, receiving radiation therapy and hormone receptor-positive disease. Among women with stage IV disease, those who underwent surgery of their primary had a 51% decreased risk of death compared with those who did not undergo surgery (HR = 0.489, 95% CI 0.339–0.704, P < 0.0001).ConclusionsAlthough IBC is an aggressive subtype of locally advanced breast cancer, it is heterogeneous with various factors affecting survival. Furthermore, our results indicate that a subgroup of women with stage IV IBC may benefit from aggressive combined modality management.     

Efficacy of Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in ER-positive Breast Cancer: Results From a Prospective Institutional Database

BackgroundAlthough neoadjuvant chemotherapy (NACT) has been established as a standard for medically fit patients with locally advanced breast cancer, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Rates of pathologic complete response (pCR) are known to be low, but data regarding down-staging and long-term outcomes are inconsistent.Patients and MethodsA prospective institutional database of patients with breast cancer treated with neoadjuvant therapy from 2012 to 2017 was analyzed to identify patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Patients who received NET were compared with those who received NACT. A matched analysis (age, stage, grade) was performed to compare rates of down-staging, pCR, breast conserving surgery, and CPS+EG scores.ResultsA total of 176 patients met eligibility criteria. Of these, 111 (63%) patients received NACT, 51 (29%) received NET, and 14 (8%) received both sequentially. Women prescribed NET were older (65.5 vs. 51.2 years; P < .0001) and presented with lower clinical stage (P < .0001). The median duration of NET was 90 days. When matched, clinical down-staging was more frequent with NACT (20/51; 39%) compared with NET (11/51; 22%) (P = .032). Of these, 2% achieved pCR in each cohort. Conversion rates to breast conserving surgery eligibility were low (8% and 13% with NET and NACT; P = .70). No significant differences in CPS+EG scores were identified.ConclusionsSignificantly higher rates of down-staging were achieved with NACT compared with NET when patients were matched. This study highlights the importance of establishing tumor biology and the need for biomarkers that can be used as predictive tools to inform treatment.     

A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada—Clinical Trials Group Trial,MA.12)

BackgroundIn the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear.Patients and methodsPremenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy.ResultsMedian follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices.ConclusionsAdjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.     

Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability

Previous studies have demonstrated that both anastrozole and letrozole are well tolerated. Letrozole suppresses estrogen to a greater degree than anastrozole in the serum and breast tumor. Concerns have been raised that greater potency may adversely affect patients?? quality of life (QOL). One hundred eighty-one postmenopausal women with invasive estrogen receptor-positive breast cancers were randomized to receive either 12 weeks of letrozole followed by 12 weeks of anastrozole or the reverse sequence. One hundred and six received immediate adjuvant aromatase inhibitors (AIs) following surgery, and 75 received extended adjuvant therapy. The Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-B-ES) QOL questionnaires were completed to assess QOL on each drug. Additional side-effect profiles were collected. Each patient completed a patient preference form. Twenty-one patients withdrew before study end, 10/179 (5.6%) while taking letrozole and 4/173 (2.3%) while taking anastrozole (P = 0.12). Tamoxifen-naïve patients had a higher mean ES (endocrine symptoms subscale) score at entry versus those having extended therapy (66.0 vs. 61.9; P = 0.001). There was no significant change in FACT-B-ES (overall) scores or ES scores while patients were taking anastrozole or letrozole and no significant differences between drugs. Nearly 80% of patients reported one or more side effects with either agent. No differences in frequency, grade, or range of side effects were seen between drugs. Of 160 patients, 49 (30.6%) preferred letrozole, 57 (35.6%) preferred anastrozole, and 54 (33.8%) had no preference (P = 0.26, Pearson??s Chi-squared test). In conclusion, both AIs are equally well tolerated. There were no significant differences in QOL scores between the two drugs.     

Race as an Independent Risk Factor for Breast Cancer Survival: Breast Cancer Outcomes From the Medical College of Georgia Tumor Registry

BackgroundCauses of racial disparities in breast cancer survival remain unclear. This study assesses overall survival (OS) after diagnosis between black and white women and examines factors that might correlate with this disparity.Patients and MethodsData were obtained from the Medical College of Georgia Tumor Registry. Cases included those diagnosed between 1990 and 2005. We analyzed race, stage, age of diagnosis, and treatment received: chemotherapy, radiation, surgery, and hormonal therapy. A Cox proportional hazards model was used to determine differences in OS.ResultsCompared with 670 white women, 489 black women were more likely to be younger, have later-stage disease at diagnosis, and were less likely to have received hormonal therapy. Both groups received similar rates of radiation, surgery, and chemotherapy. Black women had significantly poorer OS (adjusted hazard ratio, 1.35; 95% CI, 1.12–1.63). White women had a 5-year OS of 54% compared with 45% in black women (P = .0031). Having received radiation, surgery, or chemotherapy was not associated with OS. White women were more likely to have received hormonal therapy, which had a significant protective effect. However, a stratified analysis (between those who received hormonal therapy and those who did not) showed similar results, whereas black women experienced poorer OS in both strata.ConclusionBlack women with breast cancer had a significantly poorer OS compared with white women. White women received more hormonal therapy, which had a protective effect. There were no differences in treatment received regarding radiation, surgery, or chemotherapy, and these treatments were not associated with OS. The reasons for racial disparities in breast cancer OS remain complex.     

Small-Cell Carcinoma of the Prostate: Report of Outcomes of Localized Disease Using the National Cancer Database

BackgroundSmall-cell carcinoma of the prostate (SCCP) is a rare but aggressive prostate cancer histology. We studied the reported comparative outcomes of the efficacy of radiotherapy (RT) versus surgery for nonmetastatic SCCP.MethodsThe National Cancer Database (NCDB) was queried for nonmetastatic disease diagnosed from 2004 to 2015 as SCCP (defined as having a component of SCCP) receiving a single definitive local control modality (RT or surgery).ResultsA total of 243 patients were included (177 RT and 66 surgery). A total of 142 patients received chemotherapy (CHT). Mean age was 68 years. One hundred forty patients had adenocarcinoma concurrently with the SCCP while 103 patients had pure histology. For pure histology, multivariable analysis (MVA) showed nonacademic facility, stage 4 disease, and poorly differentiated grade were associated with worse survival. On MVA, receipt of CHT (hazard ratio [HR] = 0.84, P = .644) or receipt of androgen deprivation therapy (HR = 0.88, P = .715) did not affect overall survival. Receipt of RT was nonsignificant compared to surgery (HR = 0.75, P = .475). For mixed histology, MVA showed receipt of CHT and prostate-specific antigen > 20 ng/mL were associated with worse survival. Receipt of androgen deprivation therapy (HR = 1.35, P = .414) did not affect overall survival. Receipt of RT was also nonsignificant compared to surgery (HR = 1.42, P = .344).ConclusionRT and surgery for nonmetastatic SCCP yield comparable options as local therapies.     

Radiotherapy for Stage III Non–Small-Cell Lung Carcinoma in the Elderly (Age ≥ 70 years)

BackgroundElderly patients are underrepresented in trials that establish definitive chemoradiotherapy as the standard of care for inoperable stage III non–small-cell lung carcinoma (NSCLC). This study analyzed radiotherapy treatment delivery and outcomes at our institution according to elderly (≥ 70 years old) or younger (< 70 years) age.MethodsRecords of patients who received radiotherapy for stage III NSCLC between January 1998 and February 2010 were reviewed. Factors analyzed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), weight loss, radiation therapy intent, and chemotherapy administered.ResultsA total of 189 patients with stage III NSCLC were analyzed (age range, 28-92 years). Elderly patients (n = 86) were more likely to have ECOG PS ≥ 2 (P < .05) and receive palliative treatment (P < .05). Elderly patients less often received concurrent chemoradiotherapy (P < .05) as well as cisplatin (P < .05). Median survival was 10.3 months for elderly patients compared with 17.2 months for younger patients (P < .05 ). In addition, elderly patients with ECOG PS (P < .05) as well as those who received definitive concurrent chemoradiotherapy (P < .05) had inferior outcomes compared with otherwise similar younger patients. However, on multivariate analysis, elderly age was not associated (P = .428) with increased risk of death, whereas poor ECOG PS (≥ 2) was significant (P < .05). In elderly patients, definitive treatment (P < .05), chemotherapy administration (P < .05), and ECOG PS of 0-1 (P < .05) were associated with improved outcome.ConclusionsAlthough elderly patients with stage III NSCLC experience inferior outcomes than younger patients with comparable disease, they are also more likely to receive suboptimal therapy. On multivariate analysis, advanced age was not associated with worse survival, which indicates that appropriately selected elderly patients should receive definitive chemoradiotherapy.     

Real-World Experience with CDK4/6 Inhibitors for Metastatic HR+/HER2− Breast Cancer at a Single Cancer Center

BackgroundA study was initiated at Roswell Park Comprehensive Cancer Center to capture the real-world experience related to the use of CDK4/6 inhibitors (Ciclibs) for the treatment of metastatic hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-).Patients and MethodsA total of 222 patients were evaluated who received CDK4/6 inhibitors in the period from 2015 to 2021. Detailed clinical and demographic information was obtained on each patient and used to define clinical and demographic features associated with progression-free survival on CDK4/6 inhibitor-based therapies.ResultsIn this real-world analysis, the majority of patients received palbociclib as the CDK4/6 inhibitor with letrozole or fulvestrant as the predominant endocrine therapies. The median progression-free survival (PFS) in the letrozole (27.6 months) and fulvestrant (17.2 months) groups were comparable to that observed in clinical trials. As expected, age at start of the treatment and menopausal status influenced endocrine therapy utilization but were not associated with PFS. Patients with recurrent disease had shorter PFS (P = .0024) than those presenting with de novo metastasis. The presence of visceral metastasis trended toward shorter PFS (P = .051). Similarly, prior endocrine therapy (P = .003) or chemotherapy (P = .036) was associated with shorter PFS. Body mass index was not associated with PFS or with dose interruption and/or modification. While the number of minorities in this analysis is limited (n = 26), these patients as a group had statistically shorter PFS on treatment (P = .002).ConclusionsThe real-world progression-free survival with CDK4/6 inhibitors mimics that observed in the clinical trial. A number of clinical and demographic features were associated with PFS on CDK4/6 inhibitor-based therapy. Further studies are ongoing to validate these findings incorporating additional cancer centers.

This article reports a real-world experience related to the use of CDK4/6 inhibitors for the treatment of metastatic hormone receptor-positive and HER2-negative breast cancer, focusing on clinical and demographic features associated with progression-free survival.

Implications for PracticeThis study provides the real-world experience with the use of CDK4/6 inhibitors in the treatment of metastatic HR+/HER2− breast cancer. The work defines clinical and demographic features that impact the response to these agents and could offer guidance in preferred strategies for select manifestations of the disease. The study also suggests the need for more study of under-represented minority populations.     

Age and competing concerns in treatment selection for women with non-metastatic HR+ and HER2- breast cancer: Current clinical practice

BackgroundNewer adjuvant treatment options for non-metastatic breast cancer have increased survival. There is a need to investigate whether demographic and clinical characteristics of women with hormone receptor-positive, human epidermal growth receptor 2-negative non-metastatic breast cancer (stages I-III) differentially influence treatment decisions in older (age 65 or older) versus younger patients (under age 65).MethodsIn a retrospective electronic medical record review, prevalence ratio with 95% confidence interval for treatment decisions in older vs younger patients was calculated using log binomial regression adjusted for race, stage, and total number of comorbidities.ResultsIn a sample of 537 patients, 66% were age < 65 and 34% age ≥ 65. Older patients included a higher proportion of White women (85% vs 75%, P = .02), higher number of comorbidities (P ≤0.0001), and lower stage tumors (P = .0004). In multivariable analysis, age ≥ 65 was independently associated with fewer mastectomies (95% CI 0.65–0.96, P = .02), more lumpectomies (95% CI 1.05–1.42, P = .01), and less receipt of radiation treatment (95% CI 0.78–0.97, P = .01) and/or chemotherapy (95% CI 0.73–0.95, P = .006). In multivariate analysis, stage was independently significant for all treatment modalities, except endocrine therapy, and race was not.ConclusionsThis study suggests that age, in addition to breast cancer stage, is a predictor of treatment modality, independent of race and number of comorbidities. Treatment modality reflects a combination of patient preference and clinician assessment of fitness for current standard of care.     

Association of race with receipt of definitive therapy for high risk prostate cancer in older men

ObjectivesBlack men are more likely to die of prostate cancer (PCa) than White men. Whether this difference is driven by biological versus sociodemographic and access to care differences is actively investigated. However, studies that have highlighted racial disparities in PCa outcomes have been poorly represented by elderly men, a notoriously undertreated group. Herein, we evaluated use of curative treatment between Black and White elderly men with aggressive PCa in a large US database.MethodsMen ≥80 years diagnosed with National Comprehensive Cancer Network-defined high risk PCa between 2004 and 2016 were analyzed from the National Cancer Database. Multivariable logistic regression was used to model the effect of race and sociodemographic factors on receipt of definitive therapy (surgery or radiation +/− androgen deprivation therapy [ADT]) versus non-definitive therapy (ADT alone or observation) in inverse probability weighted groups matched for stage, prostate-specific antigen, and Gleason score.ResultsBetween 2004 and 2016, utilization of definitive therapy with either surgery or radiation therapy increased in both White and Black men in the United States. However, we found that Black men compared with White men were significantly less likely to receive definitive therapy (OR 0.71, 95% CI 0.64–0.79, p < .001). Using multivariable modeling, effect size diminished after adjusting for sociodemographic variables. Notably, there is evidence of the racial disparity narrowing over time.ConclusionsThese findings highlight striking but improving racial disparities in elderly men with high risk PCa in the US, an overall undertreated population.     

Small-cell Lung Cancer in Very Elderly (≥ 80 Years) Patients

BackgroundThis analysis was performed to describe the outcome of very elderly (≥ 80 years) patients with small-cell lung cancer (SCLC) as there is no published data regarding these patients.Materials and MethodsOne hundred forty-six very elderly patients with SCLC were identified from the Institutional Lung Cancer Database ranging in age from 80 to 92 years (median, 82 years). Of these, 47 (32%) patients had limited-stage SCLC (L-SCLC), and 99 (68%) had extensive-stage SCLC (E-SCLC). All were Caucasian, and the majority (64%) were female. Sixty-seven (46%) patients had Zubrod performance status (PS) of 0 to 1.ResultsOf the 146 patients, 44 (30%) received no therapy, 65 (45%) received chemotherapy alone, 27 (19%) received chemotherapy plus local therapy (thoracic radiotherapy [TRT] or surgery), and 10 (7%) received local therapy alone. The median survival was 5.4 months. On univariable analysis, age (P = .019), stage (L-SCLC vs. E-SCLC; P = .0002), PS (P < .0001), and treatment option (P < .0001) were associated with survival. On multivariable analysis, stage (P = .011), PS (P = .029), and treatment option (P < .0001) maintained significance. For entire cohort, the median survival was 1.3 months without active therapy, 6 months with local therapy alone, 7.2 months with chemotherapy alone, and 14.4 months with chemotherapy plus local therapy (P < .0001, univariable and multivariable). Similar survival findings in response to treatment were found when the L-SCLC and E-SCLC cohorts were separately analyzed.ConclusionsThe survival of very elderly patients with SCLC was associated with stage (L-SCLC vs. E-SCLC), PS, and treatment option. Very elderly patients with SCLC often have limited functional reserve required to tolerate aggressive multimodality therapy but appeared to benefit from it. Geriatric assessments, careful monitoring, and extra support are warranted in elderly patients. Care should be individualized based on the desires and needs of each patient.     

Who Benefits the Most From Adjuvant Durvalumab After Chemoradiotherapy for Non-small Cell Lung Cancer? An Exploratory Analysis

PurposeAdjuvant durvalumab is now recommended for most patients with locally advanced non-small cell lung cancer after concurrent chemoradiotherapy. Herein, we explore the clinical factors that may be associated with the benefit from adjuvant durvalumab.Methods and MaterialsPatients with non-small cell lung cancer who were treated with definitive concurrent chemoradiotherapy at our institution between August 2013 and May 2019 were included in this analysis. Clinical and treatment characteristics were tested for associations with progression-free survival (PFS) in Cox models. Interaction terms were added to the PFS Cox models to explore factors that may modulate the effects of adjuvant durvalumab. PFS and overall survival (OS) rates were estimated using the Kaplan-Meier method, and comparisons between patient subgroups were performed using log rank testing.ResultsA total of 105 patients met the eligibility criteria. Thirty-five patients (33%) received adjuvant durvalumab. Treatment with durvalumab was associated with significant improvement in PFS (1-year PFS: 67% vs 39%; log rank P = .006) and OS (1-year OS: 88% vs 76%; log rank P = .041). Exploratory analyses identified the neutrophil-to-lymphocyte ratio (NLR) after radiation therapy (RT) as a factor that may be associated with a benefit from durvalumab. For patients with post-RT NLR exceeding the cohort’s median value of 4.3, receipt of adjuvant durvalumab was not associated with a significant PFS improvement (1-year PFS: 45% vs 36%; log rank P = .702). For patients with post-RT NLR <4.3, durvalumab receipt was associated with improved PFS (69% vs 41%; P = .009). High mean RT doses delivered to the heart and esophagus were associated with high post-RT NLR.ConclusionsWe identified low NLR after chemoradiotherapy as a factor that may be associated with a benefit from adjuvant durvalumab. Validation studies are warranted.     

COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial,assessing the incidence of arthralgia,and compliance within the first year of adjuvant anastrozole therapy

BackgroundThis prospective study evaluated the relationship between arthralgia and compliance during the first year of adjuvant anastrozole therapy in postmenopausal women with hormone receptor-positive early breast cancer.Patients and methodsCOMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open-label, multicenter, noninterventional study conducted in Germany. Patients had started adjuvant anastrozole 3–6 months before the study start. The primary end points were arthralgia, compliance, and the relationship between compliance and arthralgia, assessed at specific time points.ResultsOverall, 1916 patients received upfront anastrozole. Mean arthralgia scores were increased from baseline at each visit up to 9 months. Compliance with anastrozole therapy gradually decreased over time from baseline to 9 months (P < 0.001). At 9 months, investigators estimated that >95% of patients were compliant versus patient reports of <70%. There was a significant association between arthralgia mean scores and noncompliance at 6 months (P < 0.0001), 9 months (P < 0.0001), and overall (P < 0.0001). Over time, new events or impairment of existing arthralgias were reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients.ConclusionArthralgia is important in the clinical management of women with early breast cancer and may contribute to noncompliance and clinical outcomes.ClinicalTrials.gov identifierNCT00857012.     

Analysis of the Safety and Pregnancy Outcomes of Fertility-sparing Surgery in Ovarian Malignant Sex Cord-stromal Tumours: A Multicentre Retrospective Study

AimsTo assess the difference in survival between fertility-sparing surgery (FSS) and radical surgery and explore pregnancy outcomes after FSS in stage I malignant sex cord-stromal tumours (MSCSTs).Materials and methodsWe carried out a multicentre retrospective cohort study on patients who were diagnosed with MSCSTs and the tumour was confined to one ovary. The patients were divided into FSS and radical surgery groups. Inverse probability of treatment weighting (IPTW) was used to balance variables between the two groups. Kaplan–Meier analysis was used to compare the difference in disease-free survival (DFS). Univariate and multivariate Cox regression analysis was used to find risk factors of DFS. Univariate logistic regression analysis was used to assess risk factors of pregnancy.ResultsIn total, 107 patients were included, of whom 54 (50.5%) women underwent FSS and 53 (49.5%) received radical surgery. After IPTW, a pseudo-population of 208 was determined and all of the covariates were well balanced. After a median follow-up time of 50 months (range 7–156 months), 10 patients experienced recurrence and two died. There was no significant difference in DFS between the two groups, both in unweighted (P = 0.969) or weighted cohorts (P = 0.792). In the weighted cohort, stage IC (P = 0.014), tumour diameter >8 cm (P = 0.003), incomplete staging surgery (P = 0.003) and no adjuvant chemotherapy (P < 0.001) were the four high-risk factors associated with a shorter DFS. Among 14 patients who had pregnancy desire, 11 (78.6%) women conceived successfully; the live birth rate was 76.9%. In univariate analysis, only adjuvant chemotherapy (P = 0.009) was associated with infertility.ConclusionsOn the premise of complete staging surgery, FSS is safe and feasible in early stage MSCSTs with satisfactory reproductive outcomes.     

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma,Plasma Cell Leukemia and Extramedullary Myeloma

BackgroundPatients with advanced/aggressive multiple myeloma have limited treatment options to achieve rapid disease control. In eligible patients, bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide is often used. However, many patients are refractory to or have toxicities from bortezomib and there is a need for bridging therapy. We have used a modified regimen incorporating the second-generation proteasome inhibitor carfilzomib (carfilzomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide [KD-PACE]) instead of bortezomib for relapsed/refractory multiple myeloma.Patients and MethodsThis 2-center retrospective study included consecutive patients receiving KD-PACE for relapsed or refractory multiple myeloma, plasma cell leukemia, or extramedullary myeloma. The primary outcome was the feasibility of KD-PACE as a bridging therapy to a more definitive treatment option.ResultsFifty-two patients were included. The median age was 57 years, and 67% were male. Thirty-one patients were bridged with KD-PACE to autologous hematopoietic stem cell transplant (29%), allogenic hematopoietic stem cell transplant (27%), or a clinical trial (12%). Patients bridged to autologous hematopoietic stem cell transplant, allogenic hematopoietic stem cell transplant, or a clinical trial had a superior progression-free survival (8.3 months vs 2.3 months in the nonbridged group; P < .001) and overall survival (median, 16.7 months vs 4.3 months in the nonbridged group; P < .001). No unexpected toxicities occurred from the treatment regimen.ConclusionKD-PACE is a promising treatment option for select patients with advanced/aggressive forms of myeloma requiring rapid disease control before a more definitive salvage therapy such as auto/allotransplantation or a clinical trial.     

Observational cohort study to determine the degree and causes of variation in the rate of surgery or primary endocrine therapy in older women with operable breast cancer

BackgroundIn the UK there is variation in the treatment of older women with breast cancer, with up to 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and patient choice may explain some variation in practice but clinician preference may also be important.MethodsA multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making preference) were analysed to identify whether treatment variation persisted following case-mix adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, co-morbidity, tumour stage and grade. Concordance between patients’ preferred and actual decision-making style was assessed and associations between age, treatment and decision-making style calculated.ResultsWomen (median age 77, range 70–102) were recruited from 56 UK breast units between 2013 and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56 units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients (42.2% vs 28.4%, p < 0.001).ConclusionsThis study demonstrates variation in treatment selection thresholds for older women with breast cancer. Health stratified guidelines on thresholds for PET would help reduce variation, although patient preference should still be respected.     

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma

BackgroundTo investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC).Patients and methodsA series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan–Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5–48).ResultsNeoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005).ConclusionIn this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.     

Place de la radiothérapie dans le traitement conservateur des sarcomes en territoire irradié

PurposeTo describe long-term outcome after combined-modality treatment including radiation therapy in patients with localized sarcoma within irradiated field.Patients and methodsIndividual clinical data from all consecutive patients diagnosed and treated for a localized sarcoma within irradiated field between January 2000 and October 2011 at the Institut Claudius-Regaud, Toulouse, France, were retrospectively reviewed.ResultsTwenty-seven patients were eligible for this study. Ten patients were re-irradiated with a rate of unresectable, gross or microscopically positive margins disease significantly higher than the rest of the cohort (90% vs. 12%; P < 0.001). After a median follow-up of 3.8 years, there is a non-significant trend toward longer 4-year relapse free survival in the subgroup of patients who received adjuvant or definitive radiation therapy compared to the rest of the cohort (53% vs. 27%; P = 0.09) with an acceptable toxicity profile allowing conservative management.ConclusionThe complete surgical resection sarcoma within irradiated field is often difficult to achieve enhancing the risk of relapse. Radiation therapy should be discussed when faced with an unresectable tumour or after suboptimal surgery as part of intensified local management with a curative intent.     

Validating the SumMean 18F-FDG PET Textural Feature as a Prognostic Marker in an Independent Cohort of Locally Advanced Non-Small Cell Lung Cancer Patients Undergoing Concurrent Chemoradiation Therapy

PurposeAnalyses from the ACRIN6668/RTOG0235 trial data identified the SumMean textural feature, calculated from 18-fluorodeoxyglucose positron emission tomography for tumors with a metabolic tumor volume >93 cm³, as a predictor of overall survival (OS) for patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiation therapy. Here, we validated that finding in a completely independent patient cohort from a single institution.Methods and MaterialsWe identified patients with LA-NSCLC who underwent staging 18-fluorodeoxyglucose positron emission tomography and received definitive chemoradiation therapy at our institution between 2007 and 2018. Primary tumors were segmented semiautomatically, and SumMean score was calculated for each tumor and categorized according to the previously proposed cutoff of 0.018. In patients with metabolic tumor volume >93 cm³, SumMean was evaluated as a predictor of progression-free survival (PFS) and OS using log rank and Cox proportional hazards testing.ResultsOne hundred forty-eight patients met inclusion criteria, and 34 had large tumors (>93 cm³). Twelve (35%) had high SumMean, and 22 (65%) had low SumMean. SumMean was not significantly associated with other clinical variables. Median PFS for patients with large tumors and low SumMean was 5.8 months, compared with 41.1 months for patients with large tumors and high SumMean (log rank P = .022). Median OS for patients with large tumors and low SumMean was 15.0 months; median OS was not reached for patients with large tumors and high SumMean (log rank P = .014). In multivariable analysis, high SumMean was an independent predictor of improved OS (hazard ratio, 0.26; 95% confidence interval, 0.07-0.94; P = .041) and PFS (hazard ratio, 0.30; 95% confidence interval, 0.10-0.86; P = .026).ConclusionsWe externally validated SumMean as a prognostic marker for patients with LA-NSCLC treated with chemoradiation therapy in an independent patient cohort. Future studies will explore potential mechanisms for this association and how textural features may help guide treatment decisions.     

Radiation therapy for sinonasal inverted papilloma

PurposeWe retrospectively reviewed long-term outcomes of patients with inverted papilloma (IP) treated with radiation therapy at our institution.Methods and MaterialsFrom 1969 to 2008, 13 patients with advanced or recurrent IP (n = 12) or cylindrical papilloma (n = 1) were treated with radiation therapy. The median age at radiation therapy was 53 years old (range, 32-84). Nine patients received postoperative radiation therapy, 3 received definitive radiation therapy, and 1 received preoperative radiation therapy. Of the 10 patients treated with combined-modality treatment, 1 underwent craniofacial resection and 9 underwent open resection. Eight patients, 4 patients, and 1 patient received once-daily fractionation, twice-daily fractionation, and planned split-course radiation therapy, respectively, to a median dose of 65 Gy (range, 45.3-70.4 Gy).ResultsThe median follow-up was 16.2 years. Actuarial 15-year overall and cause-specific survival rates were 62% and 82%. Fifteen-year actuarial local and regional control rates were 45% and 73%. Fifteen-year local-regional control rates for IP alone and IP associated with squamous cell carcinoma (IP-SCC) at the time of treatment were 80% and 16%. Fifteen-year overall survival rates for IP alone and IP-SCC were 40% and 50%. The only severe treatment complication was a grade 3 central nervous system radionecrosis. The most common grade 1-2 toxicities were mucositis (61%), pain (46%), conjunctivitis (31%), xerostomia (31%), epiphora (31%), and anorexia (31%).ConclusionsWhile surgery is the primary treatment for IP, radiation therapy should be considered in patients with SCC, multiply recurrent IPs, and incompletely resectable IP. Radiation therapy is associated with a relatively low risk of severe complications. Despite more aggressive treatment, local failure remains a considerable challenge.