Elizabeth M. Nichols

Comparative Analysis of the Post-Lumpectomy Target Volume Versus the Use of Pre-Lumpectomy Tumor Volume for Early-Stage Breast Cancer: Implications for the Future

PURPOSEnThree-dimensional conformal accelerated partial breast irradiation (APBI-3D-CRT) is commonly associated with the treatment of large amounts of normal breast tissue. We hypothesized that a planning tumor volume (PTV) generation based on an expansion of the pre-lumpectomy (pre-LPC) intact tumor volume would result in smaller volumes of irradiated normal breast tissue compared with using a PTV based on the post-lumpectomy cavity (post-LPC). Use of PTVs based on the pre-LPC might also result in greater patient eligibility for APBI-3D-CRT.nnnMETHODS AND MATERIALSnForty-one early-stage breast cancers were analyzed. Preoperative imaging was used to determine a pre-LPC tumor volume. PTVs were developed in the pre- and post-LPC settings as per National Surgical Breast and Bowel Project (NSABP)-B39 guidelines. The pre- and post-LPC PTV volumes were compared and eligibility for APBI-3D-CRT determined using NSABP-B39 criteria.nnnRESULTSnThe post-LPC PTV exceeded the pre-LPC PTV in all cases. The median volume for the pre- and post-LPC PTVs were 93 cm(3) (range, 24-570 cm(3)) and 250 cm(3) (range, 45-879 cm(3)), respectively, p <0.001. The difference between pre- and post-LPC PTVs represented a median of 165 cc (range, 21-482 cc) or 16% (range, 3%-42%) of the whole breast volume. Three of 41 vs. 13 of 41 cases were ineligible for APBI-3D-CRT when using the pre- and post-LPC PTVs, respectively.nnnCONCLUSIONnPTVs based on pre-LPC tumor expansion are likely associated with reduced amounts of irradiated normal breast tissue compared with post-LPC PTVs, possibly leading to greater patient eligibility for APBI-3D-CRT. These findings support future investigation as to the feasibility of neoadjuvant APBI-3D-CRT.

Repeat Computed Tomography Simulation to Assess Lumpectomy Cavity Volume During Whole-Breast Irradiation

PURPOSEnTo determine whether the lumpectomy cavity (LPC) decreases in volume during whole-breast radiotherapy (RT) and what factors influence the decrease.nnnPATIENTS AND METHODSnForty-three women with 44 breast lesions were prospectively enrolled. Eligible patients underwent lumpectomy followed by a CT simulation (CT1) within 60 days of surgery. Patients were treated to the entire breast to a dose of 45-50.4 Gy. After 21-23 treatments, a second planning CT simulation (CT2) was done. The LPC was contoured on CT2, and the volumes (LCV) were compared between CT1 and CT2.nnnRESULTSnThe median LCV on CT1 and CT2 was 38.2 cm(3) and 21.7 cm(3), respectively. The median percent change and volume decrease between CT1 and CT2 was -32.0% and 11.2 cm(3), respectively (n = 44). The LCV decreased in 38 of 44 patients (86%). There was a significant correlation between initial LCV and decrease in volume (p = 0.001) and initial LCV and percent decrease in volume (p < 0.001). There was no correlation between time from surgery to CT1, to start of RT, or to CT2 and change in volume.nnnCONCLUSIONSnPatients who undergo lumpectomy almost always have a decrease in their LCV during whole-breast RT. There was a correlation between the initial LCV and decrease in volume on repeat CT simulation. Evaluating patients for this change can potentially lead to decreased doses of radiation to the remaining breast and other critical structures when delivering a small-field boost. Repeat CT simulation should be considered in patients with larger cavities or cavities near critical structures.

Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer

PURPOSEnFor inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population.nnnMETHODS AND MATERIALSnThe clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes.nnnRESULTSnFrom 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18xa0months). The median age and tumor size was 72xa0years and 2.5xa0cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50xa0Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7xa0months. The DFS rate was 58.3% and 53.2% at 1 and 3xa0years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3xa0months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8xa0months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0xa0months; P=.02) and OS (31.4 vs 14.3xa0months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and elsewhere lung (20.8%). The median time to each was 5 to 7xa0months.nnnCONCLUSIONSnFrom the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50xa0Gy) with chemotherapy should be considered a standard option.

Preoperative radiation therapy significantly increases patient eligibility for accelerated partial breast irradiation using 3D-conformal radiotherapy.

Introduction:Three-dimensional-conformal radiation (3D-CRT) is the most common approach used in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 for accelerated partial breast irradiation (APBI). Administration of APBI-3D-CRT in the preoperative (preop) setting has been shown to decrease the planning target volume. The impact of this decrease on patient eligibility for APBI has not been evaluated in a comparative manner. Materials and Methods:Forty patients with 41 previously treated breast cancers (⩽4 cm) were analyzed. A spherical preop tumor volume was created using the largest reported radiographic dimension and centered within the contoured lumpectomy cavity. Plans were created and optimized using the preop tumor volume and postoperative lumpectomy cavity using NSABP B-39 guidelines. The primary end point was to evaluate for differences in patient eligibility and normal tissue exposure. Results:Thirty-five tumors (85%) in the preop versus 19 tumors (46%) in the postoperative setting were eligible for 3D-CRT-APBI using NSABP B-39 criteria (P=0.0002). The most common reason for ineligibility was due to >60% of the ipsilateral breast volume receiving 50% of the dose. Other reasons included dose to the contralateral breast, heart, and ipsilateral lung. Preop 3D-CRT-APBI was associated with statistically significant improvements in dose sparing to the heart, ipsilateral normal breast tissue, contralateral breast, chest wall, ipsilateral lung, and skin. Conclusions:Dosimetrically, the use of preop radiation would increase patient eligibility for 3D-CRT-APBI and decrease dose to normal tissues, which will potentially decrease toxicity and improve cosmesis. These results provide the basis for a recently activated prospective study of preop 3D-CRT-APBI.

Neutrophil‐Lymphocyte Ratio Is a Prognostic Marker in Patients with Locally Advanced (Stage IIIA and IIIB) Non‐Small Cell Lung Cancer Treated with Combined Modality Therapy

BACKGROUNDnNeutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in localized and advanced non-small cell lung cancer (NSCLC). Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesized that low NLR at diagnosis is associated with improved overall survival (OS) in locally advanced NSCLC (LANSCLC) patients.nnnPATIENTS AND METHODSnRecords from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline demographic data and pretreatment peripheral blood absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used for multivariable analysis.nnnRESULTSnThe NLR was prognostic for OS (pu2009<u2009.0001). Median survival in months (95% confidence interval) for the first, second, third, and fourth quartile groups of the population distribution of NLR were 27 (19-36), 28 (22-34), 22 (12-31), and 10 (8-12), respectively. NLR remained prognostic for OS after adjusting for race, sex, stage, performance status, and chemoradiotherapy approach (pu2009=u2009.004).nnnCONCLUSIONnTo our knowledge, our series is the largest to demonstrate that baseline NLR is a significant prognostic indicator in LANSCLC patients who received definitive chemoradiation with or without surgery. As an indicator of inflammatory response, it should be explored as a potential predictive marker in the context of immunotherapy and radiation therapy.nnnIMPLICATIONS FOR PRACTICEnNeutrophil-lymphocyte ratio measured at the time of diagnosis was associated with improved overall survival in 276 patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) treated with definitive chemoradiation with or without surgery. To our knowledge, our series is the largest to demonstrate that baseline neutrophil-lymphocyte ratio is a significant prognostic indicator in locally advanced NSCLC patients who received definitive chemoradiation with or without surgery. Neutrophil-lymphocyte ratio is an inexpensive biomarker that may be easily utilized by clinicians at the time of locally advanced NSCLC diagnosis to help predict life expectancy.

Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC)

OBJECTIVESnTo determine the prognostic effect of Body Mass Index (BMI) in definitively treated locally advanced NSCLC patients.nnnMATERIALS AND METHODSnIn this single institution retrospective cohort study, we evaluated 291 patients who were treated for locally advanced NSCLC from 2000 to 2010. They were stratified into four BMI groups based on World Health Organization criteria: underweight (<18.5kg/m2), normal weight (18.5 to <25kg/m2), overweight (25 to <30kg/m2), and obese (≧30kg/m2). Overall survival was analyzed by BMI group.nnnRESULTSnBaseline patient characteristics and treatment parameters were similar between obese and normal weight patients. Increasing BMI was associated with improved overall survival (P=0.011), even when underweight cases were excluded. There was a sustained 31%-58% reduction in mortality of obese relative to normal weight patients (HR 0.68±0.21, 0.61±0.19, and 0.42±0.19, for each year post-treatment respectively). Statin use after diagnosis was highly associated with increasing BMI (P<0.001) and predicted improved survival in a multivariate analysis (HR 0.60, 95% CI 0.41-0.89, P=0.011).nnnCONCLUSIONnObese patients in this retrospective study had significantly improved survival relative to normal weight patients. Our data suggest that the protective effect of obesity in locally advanced NSCLC is not solely due to short-term treatment effects, decreased smoking exposure, or poor prognostic factors from underweight patients. Notably, statin use was also associated with improved survival. Additional studies are needed to clarify the mechanisms and possible concomitant factors underlying the obesity paradox in NSCLC.

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

PURPOSEnTo assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy.nnnPATIENTS AND METHODSnThis was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (<3xa0cm), N0 tumors. Patients received 38.5xa0Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed >21xa0days after radiation therapy. Adjuvant therapy was given as per standard of care.nnnRESULTSnTwenty-seven patients completed treatment. With a median follow-up of 3.6xa0years (range, 0.5-5xa0years), there have been no local or regional failures. A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment.nnnCONCLUSIONSnPreoperative 3-dimensional conformal radiation therapy-APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.

Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy) and factors influencing consideration for surgery in stage III non-small cell lung cancer

Purpose Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4u2009Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60u2009Gy) of neoadjuvant CRT prior to surgery. Methods and materials We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. Results Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. Conclusions Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

Radiation Therapy in the Elderly with Early Stage Breast Cancer: Review and Role of New Technology

In 2013, breast cancer affected 232,340 women in the US. Of these diagnoses, 52% were in women aged 65 and older. Although age is a risk factor for the development of breast cancer, women diagnosed at an older age generally have a more favorable prognosis due to often less aggressive tumor biology. Elderly women tend to have higher rates of hormone receptor positive tumors and also tumors with lower proliferative indices (Ki-67). Despite these favorable prognostic factors, breast cancer specific mortality has only decreased at a rate of 1.1% per year for women aged 75+ in comparison to 2.4% per year for women aged <50. It has been hypothesized that this is related to under-treatment of elderly patients due to increased comorbidities which can limit treatment options as well as social influences such as distance to treatment facilities and lack of transportation. Older women are less likely to be offered standard treatment including surgery, radiotherapy, chemotherapy and endocrine therapy regardless of their breast cancer stage.

Decrease of the lumpectomy cavity volume after whole-breast irradiation affects small field boost planning

To determine whether small field boost (SFB) replanning is necessary when the lumpectomy cavity (LPC) decreases during whole-breast irradiation (WBI) and what parameters might predict a change in the SFB plan. Forty patients had computed tomography (CT) simulation (CT1) within 60 days of surgery and were resimulated (CT2) after 37.8-41.4 Gy for SFB planning. A 3-field photon plan and a single en face electron plan were created on both CTs and compared. In the 26 patients who had a ≥5 cm(3) and a ≥25% decrease in lumpectomy cavity volume (LCV) between CT scans, the SFB plan using photons was different in terms of normal breast tissue volume irradiated (BTV) (p < 0.001), and field dimensions (p < 0.001). In 20/35 patients, the energy or field size changed for electron plans on CT2, but no tested characteristics predicted for a change. Less BTV was irradiated using electrons than photons in 29% (CT1) to 37% (CT2). SFB replanning needs to be individualized to each patient because of the variety of factors that can impact dosimetric planning. Replanning is recommended when using 3-field photons if the patient has experienced a ≥5 cm(3) and a ≥25% decrease in LCV during WBI. Some patients may benefit from electron SFB replanning but no tested characteristics reliably predict those who may benefit the most. The amount of BTV irradiated is less with electrons than in photon plans and this has the potential to improve cosmesis, a clinically important outcome in breast-conserving therapy.