[Show abstract][Hide abstract] ABSTRACT: These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.
Full-text · Article · Dec 2015 · Journal of the National Comprehensive Cancer Network: JNCCN
[Show abstract][Hide abstract] ABSTRACT: The relative contribution of biologic subtype to locoregional recurrence (LRR) in patients treated with neoadjuvant chemotherapy (NAC), mastectomy, and postmastectomy radiotherapy (PMRT) is not clearly defined.
233 patients with stages 2 and 3 breast cancer who received NAC, mastectomy, and PMRT between 2000 and 2009 were included: 53 % (n = 123) had HR+ (ER or PR+/HER2-), 23 % (n = 53) had HER2+ (HER2+/HR+ or HR-), and 24 % (n = 57) had triple-negative (TN) disease (HR-/HER2-). The 5-year LRR rates were estimated by Kaplan-Meier methods. Cox regression analysis was performed to evaluate covariates associated with LRR.
The median follow-up period was 62 months. A pathologic complete response (pCR) was seen in 14 % of the patients. The 5-year LRR rate was 8 % for the entire cohort. The LRR rate was 0 % for the patients with a pCR versus 9 % for the patients without a pCR (p = 0.05). TN disease [Hazard ratio (HR) 4.4; p = 0.003] and pathologic node positivity (HR 9.8; p = 0.03) were associated with LRR. Patients with TN disease had a higher LRR rate than patients with HER2+ or HR+ disease (20 vs. 6 and 4 %; p = 0.005). Among patients without a pCR, TN subtype was associated with increased LRR risk (26 versus 7 % HER+ and 4 % HR+; p < 0.001).
Patients with TN breast cancer had the highest LRR rate after NAC, mastectomy and PMRT. Whereas no LRR was observed among TN patients with a pCR, TN patients with residual disease had a significantly higher LRR risk. Patients with HR+ and HER2+ breast cancer had favorable LRR rates regardless of NAC response, likely due to receipt of adjuvant systemic targeted therapies.
No preview · Article · Aug 2015 · Annals of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.
Patients and methods:
This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method.
Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.
In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.
Full-text · Article · Jan 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Background
Human epidermal growth factor receptor 2 (HER2) overexpression was associated with locoregional recurrence (LRR) in the preadjuvant trastuzumab era. This study aimed to examine the effect of trastuzumab on LRR in mastectomy patients and whether it varied with postmastectomy radiation (PMRT).
From the authors’ institutional database, 501 women with stages I–III HER2-positive breast cancer who underwent mastectomy from 1998 to 2007 were identified. A landmark analysis was performed to compare two cohorts: 170 women who received trastuzumab and 281 who did not. Kaplan–Meier methods were used to estimate locoregional recurrence-free survival (LRRFS). A propensity score analysis was used to balance the treatment groups with respect to multiple covariates. Analogous methods were used to study the effect of PMRT.
The women in the trastuzumab group were more likely to be node positive and to receive systemic therapy or PMRT (p
No preview · Article · Jan 2015 · Annals of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Adjunct treatments for conjunctival malignancies are needed when standard therapy provides limited benefits or fails.
To describe the results of patients with diffuse conjunctival neoplasms treated with radioactive phosphorus 32 (32P)-impregnated flexible film.
This retrospective case series between January 1, 2010, and January 1, 2013, was conducted at Memorial Sloan-Kettering Cancer Center, a tertiary referral center. The study was conducted on 7 eyes of 6 patients treated for diffuse conjunctival squamous cell carcinoma, sebaceous carcinoma, or lymphoma that had recurrent or residual disease after primary treatment.
Patients underwent mapping biopsies and detailed conjunctival drawings to delineate the pathologic extent of the disease. The brachytherapy film used for treatment was the RIC Conformal Source Model 100 (RIC-100, RI Consultants). The RIC-100 is a flexible, thin (approximately 0.5-mm) film made of a polymer chemically bound to 32P. The radioactive 32P film was placed intraoperatively, allowed to stay in place until the prescription dose was reached, and then removed. The median dose at the prescription point (1 mm from the surface of the film) was 15 Gy (range, 5-17 Gy).
Patients were tested for best-corrected visual acuity, recurrence-free survival, and adverse events scored by using the Adult Comorbidity Evaluation-27 scale.
Between 2010 and 2013, 7 eyes of 6 patients were treated. The median age of patients was 70 years. All patients had a recurrent or persistent neoplasm. Four patients with squamous cell carcinoma, 1 with sebaceous carcinoma, and 1 with metachronous bilateral lymphomas were treated. The median treatment time was 19 minutes (range, 10-52 minutes). The median follow-up was 24.9 months (range, 3.1-38.2 months). Recurrence-free survival 24 months after brachytherapy was 75% (95% CI, 19-89.1). Two moderate adverse events and 1 severe adverse event occurred. Visual acuity was stable or improved in 5 of the 7 eyes (ie, better than 20/70 in the 5 patients who retained their treated eye).
Our results show the use of an intraoperative high-dose rate of 32P brachytherapy in selected cases of recalcitrant diffuse conjunctival neoplasms. This technique offers a novel adjunct in the treatment of these cancers. Further follow-up and study are warranted.
No preview · Article · Dec 2014 · Jama Ophthalmology
[Show abstract][Hide abstract] ABSTRACT: Background
Breast radiation therapy (RT) is a care standard following breast-conservation surgery (BCS), improving local control and survival in women. But in 2004, a Phase III trial demonstrated radiation following BCS provides no survival and limited local control benefit to women aged ≥70 with Stage I, estrogen receptor–positive cancers, who receive endocrine therapy (ET).This led to BCS+ET alone being incorporated as a Category I option in National Comprehensive Cancer Network (NCCN) Guidelines in 2004 for older women. We examined factors associated with change in radiation use in elderly patients at 13 NCCN centers.
We identified women treated at NCCN centers meeting age and stage criteria, during 2000-2009. Factors considered a priori potentially associated with RT use were evaluated in univariate and multivariable models, including year of diagnosis, tumor and patient characteristics, axillary surgery, and treating institution. Date of diagnosis was classified as 2000-2004 vs 2005-2009, reflecting when guidelines changed.
Among 1292 eligible cases, 78% received RT. In multivariable analysis, diagnosis after 2004 (P=0.0003), older age (P<0.0001), higher co-morbidity score (P=0.0006), smaller tumors (P=0.0146), and omission of axillary surgery (P<0.0001) predicted RT omission. 94% of women aged 70-74 received RT in 2000, compared with 88% in 2009. For the same times and age ≥80 RT use was 80% vs 41%. Finally, RT use was associated with treating institution (P<0.0001).
Following guideline changes for RT use in older women, NCCN centers demonstrated wide variation in implementing change. This suggests other factors are also influencing guideline uptake.
No preview · Article · Oct 2014 · Journal of the American College of Surgeons
[Show abstract][Hide abstract] ABSTRACT: Background: Postmastectomy radiation therapy is increasingly indicated in patients with node-positive breast cancer. The authors prospectively evaluated long-term outcomes in patients with two-stage implant-based reconstruction and postmastectomy radiation therapy to the permanent implant. Methods: A cohort of 1415 patients operated on by a single surgeon from 1998 to 2010 was evaluated annually. Outcomes were recorded prospectively. Complication rates were compared between irradiated and nonirradiated implants, including reconstructive failure (implant loss), complications (e. g., capsular contracture), aesthetic results, and satisfaction. Predicted implant loss and replacement rates were examined by irradiation status with Kaplan-Meier analysis and the log-rank test. Results: A total of 2133 breast implant reconstructions with a mean follow-up of 56.8 months (range, 12 to 164 months) were included. Three hundred nineteen implants received radiation. Implant loss occurred in 9.1 percent of irradiated implants and 0.5 percent of nonirradiated implants (p < 0.01). Capsular contracture grade IV was present in 6.9 percent of irradiated and 0.5 percent of nonirradiated implants (p < 0.01). There was no difference between groups regarding implant replacement. Ninety-two percent of irradiated patients had good to excellent aesthetic result, and 94.2 percent would choose implants again. Predicted implant loss rates were 17.5 percent and 2.0 percent for irradiated and nonirradiated implants, respectively, at 12 years (p < 0.01), and predicted implant replacement rates were 12.7 percent and 8.8 percent, respectively, at 8 years (p = not significant). Conclusions: This is the largest prospective long-term outcomes evaluation in women with immediate tissue expander/implant reconstruction and postmastectomy radiation therapy. Most patients had a good to excellent aesthetic result and preserve their reconstruction at 12 years.
No preview · Article · Oct 2014 · Plastic & Reconstructive Surgery
[Show abstract][Hide abstract] ABSTRACT: Aims
Radiation Therapy Oncology Group 98-04 sought to identify women with ‘good risk’ ductal carcinoma in situ (DCIS) who receive no significant benefit from radiation. Enrolment criteria excluded close or positive margins and grade 3 disease. To ensure reproducibility in identifying good risk pathology, an optional web based teaching tool was developed and a random sampling of 10% of submitted slides were reviewed by a central pathologist.
Submitting pathologists were asked to use the web based teaching tool and submit an assessment of the tool along with the pathology specimen form and DCIS H&E stained slide. Per protocol pathology was centrally reviewed for 10% of the cases.
Of the 55 DCIS cases reviewed, three had close or positive margins and three were assessed to include grade 3 DCIS, therefore 95% of DCIS cases reviewed were correctly graded, and 89% reviewed were pathologically appropriate for enrolment. Regarding the teaching tool, 13% of DCIS cases included forms that indicated the website was used. One of these seven who used the website submitted DCIS of grade 3.
Central review demonstrates high pathological concordance with enrolment eligibility, particularly with regard to accurate grading. The teaching tool appeared to be underused.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Plaque brachytherapy is a common form of treatment for uveal melanoma, and the Collaborative Ocular Melanoma Study (COMS) used (125)I. Recently, (106)Ru has been reintroduced for plaque brachytherapy in the United States. We reviewed our experience treating uveal melanoma with (106)Ru plaque brachytherapy using COMS planning techniques, hypothesizing that we would observe similar outcomes to those in the COMS.
Methods and materials:
Medical records of patients undergoing (106)Ru plaque brachytherapy were reviewed retrospectively. Patient, tumor, and treatment characteristics were recorded. Outcomes including visual acuity, local tumor recurrence, salvage treatment, metastasis, and survival were recorded. Cox regression analyses were used to determine factors associated with local tumor recurrence and enucleation.
Twenty-eight patients were studied. Median age was 60 years, and 50% were men. Median tumor base diameter and height were 9.4 and 2.6 mm, respectively. Ophthalmic complications were rare. Local tumor recurrence and enucleation occurred in 13 and 4 patients, respectively. Local tumor recurrence was associated with low visual acuity in the tumor-bearing eye, posterior tumors, small plaque size, and difference in plaque-tumor diameter of <6 mm. Enucleation was associated with low visual acuity and posteriorly located tumor. Estimated 5-year rate of death and metastasis was 18.5% and 11.4%, respectively.
Among patients treated with (106)Ru plaque brachytherapy using COMS planning techniques, we found a greater than expected rate of local tumor recurrence. Planning (106)Ru plaque brachytherapy should be done carefully at centers that have previously used COMS protocols and (125)I.
[Show abstract][Hide abstract] ABSTRACT: Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The NCCN Guidelines specific to management of large clinical stage II and III tumors are discussed in this article. These guidelines are the work of the members of the NCCN Breast Cancer Panel. Expert medical clinical judgment is required to apply these guidelines in the context of an individual patient to provide optimal care. Although not stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer.
Full-text · Article · Apr 2014 · Journal of the National Comprehensive Cancer Network: JNCCN
[Show abstract][Hide abstract] ABSTRACT: To determine if the presence of bilateral implants, in addition to other anatomic and treatment-related variables, affects coverage of the target volume and dose to the heart and lung in patients receiving postmastectomy radiation therapy (PMRT). A total of 197 consecutive women with breast cancer underwent mastectomy and immediate tissue expander (TE) placement, with or without exchange for a permanent implant (PI) before radiation therapy at our center. PMRT was delivered with 2 tangential beams + supraclavicular lymph node field (50Gy). Patients were grouped by implant number: 51% unilateral (100) and 49% bilateral (97). The planning target volume (PTV) (defined as implant + chest wall + nodes), heart, and ipsilateral lung were contoured and the following parameters were abstracted from dose-volume histogram (DVH) data: PTV D95% > 98%, Lung V20Gy > 30%, and Heart V25Gy > 5%. Univariate (UVA) and multivariate analyses (MVA) were performed to determine the association of variables with these parameters. The 2 groups were well balanced for implant type and volume, internal mammary node (IMN) treatment, and laterality. In the entire cohort, 90% had PTV D95% > 98%, indicating excellent coverage of the chest wall. Of the patients, 27% had high lung doses (V20Gy > 30%) and 16% had high heart doses (V25Gy > 5%). No significant factors were associated with suboptimal PTV coverage. On MVA, IMN treatment was found to be highly associated with high lung and heart doses (both p < 0.0001), but implant number was not (p = 0.54). In patients with bilateral implants, IMN treatment was the only predictor of dose to the contralateral implant (p = 0.001). In conclusion, bilateral implants do not compromise coverage of the target volume or increase lung and heart dose in patients receiving PMRT. The most important predictor of high lung and heart doses in patients with implant-based reconstruction, whether unilateral or bilateral, is treatment of the IMNs. Refinement of radiation techniques in reconstructed patients who require comprehensive nodal irradiation is warranted.
No preview · Article · Nov 2013 · Medical dosimetry: official journal of the American Association of Medical Dosimetrists
[Show abstract][Hide abstract] ABSTRACT: Radiation Therapy Oncology Group (RTOG) 95-17, a Phase II trial to evaluate multicatheter brachytherapy (mCathBrachy) as the sole method of radiation therapy for Stage I-II breast cancer (BrCa), was the first cooperative group trial in North America to evaluate accelerated partial breast irradiation (APBI) and include patient-reported outcomes (PROs). This report presents the year-5 toxicity and cosmesis data.
After lumpectomy and axillary dissection for invasive BrCa (tumor size <3cm with zero to three positive lymph nodes), 100 patients (pts), 98 evaluable, were treated (txed) with mCathBrachy from 1997 to 2000 with 34Gy administered twice daily in 10 high-dose-rate fractions or 45Gy in 3.5-6 days as a low-dose-rate implant to 1-2cm beyond the lumpectomy bed. The PROs and physician-reported outcomes of toxicity, cosmesis, and tx satisfaction at year-5 are reported here, defined as data submitted 54-78 months after tx.
Grade (G) 1-2 skin toxicity developed in 78% of the pts and G3 in 13% (no G4). The tx effects included skin dimpling/indentation (37%), fibrosis (45%), telangiectasias (45%), skin catheter marks (54%), and symptomatic fat necrosis (15%). Breast asymmetry was reported in 73%. Rates of excellent-to-good cosmesis were similar between PROs (66%) and radiation oncologists (68%). The PROs of tx satisfaction at year-5 was 75%.
RTOG 95-17 documents the year-5 skin toxicity and tx effects of mCathBrachy APBI, which are associated with PROs of good-to-excellent cosmesis and high tx satisfaction. This emphasizes the importance of PROs when assessing BrCa tx. National Surgical Adjuvant Breast and Bowel Project B39/RTOG 0413 will allow for definitive comparisons between APBI and whole breast radiation therapy.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma.
This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG).
Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes.
Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.
No preview · Article · Aug 2013 · International journal of radiation oncology, biology, physics