Cumulative Incidence Of Distant Failure Research Articles

Prognostic Importance of Nodal Microenvironment beyond Extracapsular Extension in Breast Cancer Outcomes

<h3>Purpose/Objective(s)</h3> Lymph node (LN) involvement and extracapsular extension (ECE) play important roles in breast cancer risk stratification, management, and outcome. Involvement of other axillary tissues (AXT) excised during surgery is often omitted in pathology reports and its prognostic significance is yet to be elucidated. <h3>Materials/Methods</h3> Medical records of 1,919 breast cancer patients with pathologic lymph nodes treated at our institution from 2000-2019 was retrospectively reviewed. Extensive details of LN involvement are reported by pathologists at our institution and were divided into 4 groups: LN+ only, LN+ECE, LN+AXT without ECE, and LN+ECE+AXT. AXT was defined as the involvement of lymphatic vessels, blood vessels, soft tissue metastasis, matted unspecified masses and combination of any of those forms. The primary endpoint was the impact of AXT on locoregional failure (LRF) defined as recurrence in either breast/chest wall/axilla/supraclavicular fossa, on axillary failure (AF) defined as recurrence in the axilla only and on distant failure (DF) defined as metastasis. Subgroup analysis explored the differences between types of AXT and Cox Hazard models were used. <h3>Results</h3> Among 1,919 patients analyzed, 995 had LN+ only involvement, 534 had LN+ECE, 81 had LN+AXT without ECE, and 309 had LN+ECE+AXT. The overall median follow-up was 6.5 years. The 10 years cumulative incidence of LRF was 5.9%, 6.4%, 11.8% and 10.9% in LN only, LN+ECE, LN+AXT without ECE and LN+ECE+AXT groups, respectively. The 10 years cumulative incidence of AF was 0.92%, 0.83%, 4.1% and 4.4% in LN+ only, LN+ECE, LN+AXT without ECE and LN+ECE+AXT groups, respectively. The 10 years cumulative incidence of DF was 15.7%, 23%, 23.5% and 42.1% in LN+ only, LN+ECE, LN+AXT without ECE and LN+ECE+AXT groups, respectively. On multivariable analysis controlling for number of malignant LN, ECE, tumor biology, grade and size, type of axillary surgery and radiation dose delivered to the draining lymphatics, the presence of other AXT was significantly associated with LRF (HR:2.3, P<0.01), AF (HR:4.7, P<0.01) and DF (HR: 1.4, P=0.02). ECE and number of malignant LN were not associated with LRF and AF, but rather associated with DF (HR:1.4, P=0.009 and HR:1.03, P=0.002, respectively). Delivery of 50 Gy or more to draining lymphatics was associated with better axillary control (HR:0.3, P=0.01) compared to 45 Gy. No significant difference between 45 Gy and 50 Gy to the lymphatics was observed for LRF and DF. Subgroup analysis did not show a difference between the described forms of AXT on LRF and DF. <h3>Conclusion</h3> Pathologic evaluation of the axilla's microenvironment beyond tumor deposits in lymph nodes and ECE is important to ensure adequate local control in the axilla. Given the higher risk of recurrence posed by tumor infiltration into surrounding axillary tissues, delivery of at least 50Gy to lymphatics should be considered. Our findings demonstrate the need for pathology reports to include assessment of the axilla's microenvironment.

Revised clinical and molecular risk strata define the incidence and pattern of failure in medulloblastoma following risk-adapted radiotherapy and dose-intensive chemotherapy: results from a phase III multi-institutional study.

We characterize the patterns of progression across medulloblastoma (MB) clinical risk and molecular subgroups from SJMB03, a Phase III clinical trial. One hundred and fifty-five pediatric patients with newly diagnosed MB were treated on a prospective, multi-center phase III trial of adjuvant radiotherapy (RT) and dose-intense chemotherapy with autologous stem cell transplant. Craniospinal radiotherapy to 23.4 Gy (average risk, AR) or 36-39.6 Gy (high risk, HR) was followed by conformal RT with a 1 cm clinical target volume to a cumulative dose of 55.8 Gy. Subgroup was determined using 450K DNA methylation. Progression was classified anatomically (primary site failure (PSF) +/- distant failure (DF), or isolated DF), and dosimetrically. Thirty-two patients have progressed (median follow-up 11.0 years (range, 0.3-16.5 y) for patients without progression). Anatomic failure pattern differed by clinical risk (P = .0054) and methylation subgroup (P = .0034). The 5-year cumulative incidence (CI) of PSF was 5.1% and 5.6% in AR and HR patients, respectively (P = .92), and did not differ across subgroups (P = .15). 5-year CI of DF was 7.1% vs. 28.1% for AR vs. HR (P = .0003); and 0% for WNT, 15.3% for SHH, 32.9% for G3, and 9.7% for G4 (P = .0024). Of 9 patients with PSF, 8 were within the primary site RT field and 4 represented SHH tumors. The low incidence of PSF following conformal primary site RT is comparable to prior studies using larger primary site or posterior fossa boost volumes. Distinct anatomic failure patterns across MB subgroups suggest subgroup-specific treatment strategies should be considered.

Long-term Results of a Phase I/II Trial of Nelfinavir with Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer

The objective of this Phase I/II trial was to determine the response rate by RECIST and the median overall survival (OS) of concurrent chemoradiation (CT-RT) in combination with the radiosensitizer nelfinavir in locally advanced non-small cell lung cancer (LA-NSCLC) compared to historical controls. Nelfinavir (Dose Level (DL) 1: 625 mg PO BID, DL2:1250 mg PO BID) was administered for 7 to 14 days prior to and during concurrent CT-RT to patients (pts) with biopsy confirmed unresectable IIIA and IIIB NSCLC. 23 patients (65.7%) had stage IIIA disease; 11 patients (31.4%) had stage IIIB disease; 1 patient (2.9%) had a mediastinal recurrence after resection of early stage disease. Median age was 60 years for all patients. Nineteen patients (54.2%) were male, 16 (45.7%) were female. Ten patients (28.6%) had adenocarcinoma, 16 patients (45.7%) had squamous cell carcinoma; 9 patients (25.7%) had poorly differentiated carcinoma. Patients were treated with concurrent CT-RT to a dose of 66.6/1.8Gy and cisplatinum and etoposide. DLTs were defined as any treatment related Grade 4 hematologic toxicity requiring a break in therapy or non-hematologic Grade ≥ 3 toxicity except esophagitis and pneumonitis. Protocol specified criteria for compliance included receiving greater than 80% of the prescribed RT treatments and 70% of the prescribed nelfinavir doses. Thirty-five patients were enrolled and met protocol-specified criteria for compliance, 5 at DL1 and 30 at DL2. Two patients were enrolled and did not meet protocol-specified compliance criteria are excluded from this analysis. No DLTs were observed. The recommended phase II dose of nelfinavir was 1250 mg PO BID. Median follow-up for all patients was 6.8 years and minimum follow-up for survivors was 5 years. No Grade 4 or higher non-hematologic toxicities were observed. Of the non-hematologic toxicities: 10 patients (28%) experienced Grade 3 esophagitis/dysphagia/dehydration; 4 patients (11.4%) experienced Grade 3 nausea; 3 patients (8.5%) experienced Grade 3 anorexia; 3 patients (8.5%) experienced Grade 3 fatigue; and 1 patient (3%) experienced grade 3 diarrhea and 1 patient (3%) experienced grade 3 dyspnea. 33 of the 35 patients had evaluable post-treatment CT with RECIST response rate of 94% and (31/33) stable disease rate of 6% (2/33). The cumulative incidence of local failure as site of first failure was 20%, with the median time to failure not reached (NR). The cumulative incidence of distant failure as site of first failure was 51%, with the median time to distant failure of 15.8 months. The median progression-free survival was 12 months. The median OS for all patients was 40 months; 5 year OS was 37%. Nelfinavir administered with concurrent CT-RT is associated with acceptable toxicity and very promising local control, overall response rate, and survival in unresectable LA-NSCLC. These data suggest that nelfinavir may enhance the efficacy of chemo-RT in this disease.

Patterns of Distant Failure by Intrinsic Breast Cancer Subtype in Premenopausal Women Treated With Neoadjuvant Chemotherapy

PurposeTo identify patterns of distant failure (DF) in premenopausal women receiving neoadjuvant chemotherapy (NAC) for breast cancer. Patients and MethodsPremenopausal patients treated with NAC between 2005 and 2015 at a single institution were retrospectively reviewed. Timing and location of local, regional, and distant metastases were described. Predictors for DF and overall survival (OS) were analyzed. ResultsOf 225 patients, there were 24 (10.7%) local, 30 (13.3%) regional, and 63 (28.0%) distant recurrences. Cumulative incidence of DF was higher in patients younger than age 40 (P = .01), in those with residual tumor size > 2 cm (P < .0001), in those with positive lymph nodes after NAC (P = .0003), and in those without pathologic complete response (P < .0001). Cumulative incidence of brain metastases was most common in patients with human epidermal growth factor receptor 2 (HER2)-positive disease (P = .05). Time from development of metastatic disease to death varied by breast cancer subtype (P = .019), as did 5-year OS (P = .024). Women with HER2-positive and triple-negative disease had the highest incidence of brain metastases and the shortest time from development of metastases to death. On multivariable analysis, luminal B subtype (P = .025), pathologic complete response (P = .0014), young age (P = .0008), lack of hormone therapy (P < .0001), lymphovascular space involvement (P < .0001), and pathologic size of the primary tumor (P < .0001) were all significant predictors for DF. ConclusionPatterns of DF after NAC in premenopausal women vary by breast cancer subtype, with DF more common than locoregional failure. Young age remains an independent poor prognostic factor, and OS differs by breast cancer subtype.

Outcomes after Stereotactic Body Radiotherapy for Treatment of Hepatocellular Carcinoma

Stereotactic body radiotherapy (SBRT) is an effective treatment for hepatocellular carcinoma (HCC), especially for those cases whose location, size, or distance from major vessels preclude the use of other local modalities. This study was undertaken to report the outcomes of HCC after SBRT. We reviewed the treatment characteristics and outcomes of all patients with HCC treated with SBRT between December 2005 and December 2015 at our institution. SBRT doses were converted to biologically effective doses by using a standard linear quadratic model with an α/β ratio of 10 (BED10). Disease progression was analyzed by computed tomography (CT), using the modified Response Evaluation Criteria in Solid Tumors version 1.1 and by estimation of the area of viable tumor (contrast-enhanced areas on CT). Hepatobiliary toxicities (HBT) were graded according to the Common Terminology Criteria for Adverse Events v4.0. Time-to-events were calculated from date of SBRT. A total of 42 patients were included in this study. Median age was 65.5 years (range: 48-83). Liver cirrhosis was present in 26 (61.9%) patients, 23 (54.7%) were HCV-positive and 5 (11.9%) HBV-positive. By Child-Pugh (CP) liver function classification, 30 (71.4%) patients were class A and 12 (28.6%) class B. Median tumor size was 5.1 cm (range: 1.9-12). Thirty-eight (90.4%) patients received transarterial chemoembolization prior to SBRT, with a median interval of 76 days (range: 17-2627) prior to SBRT, while 4 (9.5%) received prior radiofrequency ablation. Median SBRT dose was 40 Gy (range: 22-50) delivered with a median of 5 fractions (range: 1-5). Median follow-up was 43 months (range: 5-143). Median overall survival (OS) was 25 months (14-37, 95% I.C.), with an OS of 76% at 1y and 51% at 2y. Accounting for competing risk of death, the cumulative incidence (CI) of local failure (LF) at 1 year was 17% and 21% at 2 years. The CI of failure within the liver outside the treated region was 55% at 1 year and 64% at 2 years, and the CI of distant failure was 25% at 1 and 2 years after SBRT. Patients treated with higher SBRT doses (BED10 ≥78 Gy, n=24) showed better median OS (37 vs. 14 months, P=0.004) compared to patients receiving lower SBRT doses. Tumor size did not correlate with local control or OS rates. The incidence of acute or late G3+ HBT was of 13% for CP A and and 25% for CP B (P=NS). The most common HBT was total bilirubin elevation at serum. Six (14%) patients presented a drop in CP class at 3 months after SBRT. No case of classic radiation induced liver disease was observed. This study confirms the efficacy of SBRT for the treatment of HCC, even for large tumors, and can be safely delivered with low rates of HBT, especially for patients with preserved liver function.

Local Control Modality and Outcome for Ewing Sarcoma of the Femur: A Report From the Children's Oncology Group.

The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes. The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression. The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs ≥8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation). The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality.

Outcomes of Accelerated Hypofractionated Radiotherapy in Stage i Non-Small-Cell Lung Cancer

Outcomes after treatment with accelerated hypofractionated radiotherapy in stage i medically inoperable non-small-cell lung cancer (nsclc) patients were determined. Our single-institution retrospective review looked at medically inoperable patients with T1-2N0M0 nsclc treated with accelerated hypofractionated curative-intent radiotherapy between 1999 and 2009. Patients were staged mainly by computed tomography imaging of chest and abdomen, bone scan, and computed tomography/magnetic resonance imaging of brain. Positron-emission tomography (pet) staging was performed in 6 patients. Medical charts were reviewed to determine demographics, radiotherapy details, sites of failure, toxicity (as defined by the Common Terminology Criteria for Adverse Events, version 3.0) and vital status. The cumulative incidence of local and distant failure was calculated. Overall (os) and cause-specific (css) survival were estimated by the Kaplan-Meier method. In the 60 patients treated during the study period, the dose regimens were 50 Gy in 20 fractions (n = 6), 55 Gy in 20 fractions (n = 8), 60 Gy in 20 fractions (n = 42), and 60 Gy in 25 fractions (n = 4). All patients were treated once daily. The median follow-up was 27 months (range: 4-94 months). The os rates at 2 and 5 years were 61% [95% confidence interval (ci): 50% to 75%] and 19% (95% ci: 10% to 34%) respectively. The css rates at 2 and 5 years were 79% (95% ci: 68% to 91%) and 39% (95% ci: 24% to 63%) respectively. The cumulative incidence of local failure was 20% at 5 years. The cumulative incidence of distant failure was 28% at 5 years. No patients experienced grade 3 or greater pneumonitis or esophagitis. Accelerated hypofractionated regimens are well tolerated and provide good local control in medically inoperable patients with stage i nsclc. Such regimens may be a reasonable treatment alternative when stereotactic body radiation therapy is not feasible.

The Impact of Race and Mammographic Detection in Early Breast Cancer

The Impact of Race and Mammographic Detection in Early Breast Cancer