Shelly B. Hayes

Does Axillary Boost Increase Lymphedema Compared With Supraclavicular Radiation Alone After Breast Conservation

PURPOSE To determine independent predictors of lymphedema (LE) after breast radiotherapy and to quantify added risks of LE from regional node irradiation (RNI). MATERIALS AND METHODS A total of 2,579 women with T1-2, N 0-3, M0 breast cancer treated with breast conservation between 1970 and 2005 were studied. A total of 2,169 patients (84%) received radiation to the breast (B), 226 (8.8%) to the breast and supraclavicular LNs (B+SC), and 184 (7.1%) to the breast, supraclavicular LNs, and a posterior axillary boost (B+SC+PAB). Median follow-up was 81 months (range, 3-271). RESULTS Eighteen percent of patients developed LE. LE risks were as follows: 16% (B), 23% (B+SC), and 31% (B+SC+PAB) (p < 0.0001). LE severity was greater in patients who had RNI (p = 0.0002). On multivariate analysis, RT field (p < 0.0001), obesity index (p = 0.0157), systemic therapy (p = 0.0013), and number of LNs dissected (p < 0.0001) independently predicted for LE. In N1 patients, the addition of a SC to tangents (p < 0.0001) and the addition of a PAB to tangents (p = 0.0017) conferred greater risks of LE, but adding a PAB to B+SC RT did not (p = 0.8002). In the N2 patients, adding a PAB increased the risk of LE 4.5-fold over B+SC RT (p = 0.0011). CONCLUSIONS LE predictors included number of LNs dissected, RNI, obesity index, and systemic therapy. LE risk increased when a SC or PAB were added in the N1 subgroup. In the N2 patients, a PAB increased the risk over B+SC. The decision to boost the axilla must be weighed against the increased risk of LE that it imposes.

Parameters for Treatment Decisions for Salvage Radiation Therapy

Radical prostatectomy (RP) is the most common primary treatment for prostate cancer. About 40% of those with high-risk pathologic features, such as a positive margin or seminal vesicle involvement, will develop biochemical failure at some point in the future. Radiotherapy (RT), with or without concurrent androgen deprivation, has been used liberally in the management of men with a rising prostate-specific antigen (PSA) after RP, based mostly on relatively small retrospective series. Factors such as the prostatectomy Gleason score, seminal vesicle invasion, absolute pre-RT PSA level, and pre-RT PSA doubling time are emerging as important determinants of outcome after RT. These factors should be used as a guide to the options of local therapy alone (RT), local therapy plus systemic therapy (typically androgen deprivation therapy), and systemic therapy alone.

Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer

We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, stereotactic body RT [SBRT]) and brachytherapy (BT), with an emphasis on the outcomes, toxicities, and contraindications for therapies. PICOS/PRISMA methods were used to identify published English-language comparative studies on PubMed (from 1980 to 2015) that included men treated on prospective studies with a primary endpoint of patient outcomes, with ⩾70 patients, and ⩾5year median follow up. Twenty-six studies met inclusion criteria; of these, 16 used EBRT, and 10 used BT. Long-term freedom from biochemical failure (FFBF) rates were roughly equivalent between conventional and hypofractionated RT with intensity modulation (evidence level 1B), with 10-year FFBF rates of 45-90%, 40-60%, and 20-50% (for low-, intermediate-, and high-risk groups, respectively). SBRT had promising rates of BF, with shorter follow-up (5-year FFBF of >90% for low-risk patients). Similarly, BT (5-year FFBF for low-, intermediate-, and high-risk patients have generally been >85%, 69-97%, 63-80%, respectively) and BT+EBRT were appropriate in select patients (evidence level 1B). Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82-97%, 1-14%, 0-8%, respectively) have not been detected in randomized trials of dose escalation or in studies comparing RT modalities. Studies did not use patient-reported outcomes, through Grade 3-4 toxicities were rare (<5%) among all modalities. There was limited evidence available to compare proton therapy to other modalities. The treatment decision for a man is usually based on his risk group, ability to tolerate the procedure, convenience for the patient, and the anticipated impact on quality of life. To further personalize therapy, future trials should report (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education status; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics.

Postmastectomy radiation therapy for T3N0: A SEER analysis

There is conflicting evidence regarding the benefit of postmastectomy radiation therapy (PMRT) for pathologic stage T3N0M0 breast cancers. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the benefit of PMRT in this patient population.

Multifocal and multicentric breast cancer is associated with increased local recurrence regardless of surgery type.

Multifocal and multicentric breast cancers have been correlated with poor prognostic factors and worse outcomes versus unifocal disease. We evaluated the impact of multifocal and multicentric disease versus case controls with unifocal disease, matching for age, grade, T‐, and N‐stage. A total of 110 patients with multifocal (n = 93) or multicentric (n = 17) disease and 263 matched case controls were identified with a median follow‐up of 53 months and 64 months, respectively. The actuarial local control rates for the multifocal/multicentric and unifocal group were 88% and 97%, respectively at both 5 and 10 years (p < 0.001). On multivariate analysis, multifocal/multicentric disease remained associated with higher local recurrence after controlling for other covariates including surgery type. The disease‐free survival rates in the multifocal/multicentric group at 5 and 10 years were 75% and 71%, respectively, versus 87% and 78% at 10 years (p = 0.01). On multivariate analysis, multifocal/multicentric disease was no longer associated with worse disease‐free survival. There was no difference in the cohorts in terms of regional control, overall survival, or cancer specific survival. Our findings suggest that multifocal/multicentric disease may be associated with worse outcomes versus unifocal disease regardless of type of surgery. This suggests a more biologically aggressive cancer and may be an important consideration when managing these patients. Further studies are needed to better understand the impact of multifocal/multicentric breast cancers on outcomes.

Prostate Cancer Patients With Unmanaged Diabetes or Receiving Insulin Experience Inferior Outcomes and Toxicities After Treatment With Radiation Therapy

Micro‐Abstract We evaluated the effect of type 2 diabetes, and medications used in its management, on prostate cancer patients receiving radiation therapy. Men who were receiving insulin and those not receiving any medication had increased risk of death and toxicity than those without diabetes. Background: The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy. Patients and Methods: We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer‐specific survival, and toxicities. Kaplan–Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used. Results: Of the 3217 patients, 1295 (40%) were low‐risk, 1192 (37%) were intermediate‐risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow‐up time was 50 (range, 1‐190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66‐1.54), BF (sHR, 2.14; 0.88‐1.83), and cause‐specific mortality (sHR, 3.87; 95% CI, 1.31‐11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%‐14% vs. 2%‐6%; P < .01). Conclusion: Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients. Graphical abstract: Figure. No Caption available.

A comparison of robotic arm versus gantry linear accelerator stereotactic body radiation therapy for prostate cancer

Prostate cancer is the most prevalent cancer diagnosed in men in the United States besides skin cancer. Stereotactic body radiation therapy (SBRT; 6–15 Gy per fraction, up to 45 minutes per fraction, delivered in five fractions or less, over the course of approximately 2 weeks) is emerging as a popular treatment option for prostate cancer. The American Society for Radiation Oncology now recognizes SBRT for select low- and intermediate-risk prostate cancer patients. SBRT grew from the notion that high doses of radiation typical of brachytherapy could be delivered noninvasively using modern external-beam radiation therapy planning and delivery methods. SBRT is most commonly delivered using either a traditional gantry-mounted linear accelerator or a robotic arm-mounted linear accelerator. In this systematic review article, we compare and contrast the current clinical evidence supporting a gantry vs robotic arm SBRT for prostate cancer. The data for SBRT show encouraging and comparable results in terms of freedom from biochemical failure (>90% for low and intermediate risk at 5–7 years) and acute and late toxicity (<6% grade 3–4 late toxicities). Other outcomes (eg, overall and cancer-specific mortality) cannot be compared, given the indolent course of low-risk prostate cancer. At this time, neither SBRT device is recommended over the other for all patients; however, gantry-based SBRT machines have the abilities of treating larger volumes with conventional fractionation, shorter treatment time per fraction (~15 minutes for gantry vs ~45 minutes for robotic arm), and the ability to achieve better plans among obese patients (since they are able to use energies >6 MV). Finally, SBRT (particularly on a gantry) may also be more cost-effective than conventionally fractionated external-beam radiation therapy. Randomized controlled trials of SBRT using both technologies are underway.

Comparison of Adjuvant Radiation Therapy Alone Versus Radiation Therapy and Endocrine Therapy in Elderly Women With Early-Stage, Hormone Receptor-Positive Breast Cancer Treated With Breast-Conserving Surgery

BACKGROUND Randomized data examining adjuvant radiation therapy (RT) alone in elderly women with low-risk, hormone receptor-positive (HR(+)) breast cancer is lacking. We investigated the outcomes for elderly women treated with adjuvant RT alone versus RT plus endocrine therapy (ET) after breast-conserving surgery. PATIENTS AND METHODS We queried our institutional breast cancer database for the following patients: age > 65 years, stage T1-T2N0, HR(+), and treatment with breast-conserving surgery, including adjuvant RT. The χ(2) analysis identified significant baseline differences between the groups. Cox proportional hazard methods identified predictors of endpoints on multivariate analysis. Kaplan-Meier estimates of survival were compared using the log-rank test. RESULTS A total of 504 patients were identified, 311 had undergone RT plus ET (62%) and 193, RT alone (38%). The median follow-up time was 88 months. The RT-alone group versus RT plus ET group had different median age (72 vs.71 years, P < .001), different median tumor size (1 vs. 1.3 cm, P < .001), lower grade (40% vs. 29%, P = .05), and fewer close or positive margins (11% vs. 19%, P = .01). The adherence rate to prescribed ET was 70%. Tumor size predicted an increased risk of distant metastasis (DM) (hazard ratio, 1.96; 95% confidence interval [CI], 1.23-3.13) and worse disease-free survival (DFS) (hazard ratio, 1.86; 95% CI, 1.22-2.86). ET nonadherence versus adherence predicted for risk of DM (hazard ratio, 5.03; 95% CI, 1.98-12.66) and DFS (HR, 4.24; 95% CI, 1.9-10.3). Of the women with DM, 83.8% had tumors > 1 cm in size. CONCLUSION ET nonadherence and tumor size > 1 cm predicted an increased risk of DM and worse DFS, favoring the addition of ET in this group. However, RT alone for women with tumors less than or equal to 1 cm may be appropriate.

Splenic irradiation for splenomegaly: A systematic review

Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r2 all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.

A treatment planning comparison between a novel rotating gamma system and robotic linear accelerator based intracranial stereotactic radiosurgery/radiotherapy

To compare the dosimetric parameters of a novel rotating gamma ray system (RGS) with well-established CyberKnife system (CK) for treating malignant brain lesions. RGS has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. We compared several dosimetric parameters in 10 patients undergoing brain stereotactic radiosurgery including plan normalization, number of beams and nodes for CK and shots for RGS, collimators used, estimated treatment time, D 2 cm and conformity index (CI) among two modalities. The median plan normalization for RGS was 56.7% versus 68.5% (p  =  0.002) for CK plans. The median number of shots from RGS was 7.5 whereas the median number of beams and nodes for CK was 79.5 and 46. The median collimators diameter used was 3.5 mm for RGS as compared to 5 mm for CK (p  =  0.26). Mean D 2 cm was 5.57 Gy for CyberKnife whereas it was 3.11 Gy for RGS (p  =  0.99). For RGS plans, the median CI was 1.4 compared to 1.3 for the CK treatment plans (p  =  0.98). The average minimum and maximum doses to optic chiasm were 21 and 93 cGy for RGS as compared to 32 and 209 cGy for CK whereas these were 0.5 and 364 cGy by RGS and 18 and 399 cGy by CK to brainstem. The mean V12 Gy for brain predicting for radionecrosis with RGS was 3.75 cm3 as compared to 4.09 cm3 with the CK (p  =  0.41). The dosimetric parameters of a novel RGS with a ring type gantry are comparable with CyberKnife, allowing its use for intracranial lesions and is worth exploring in a clinical setting.