Nisha Ohri

18F-FDG PET/CT Metabolic Tumor Volume and Total Lesion Glycolysis Predict Outcome in Oropharyngeal Squamous Cell Carcinoma

Treatment of oropharyngeal squamous cell carcinoma with chemoradiotherapy can now accomplish excellent locoregional disease control, but patient overall survival (OS) remains limited by development of distant metastases (DM). We investigated the prognostic value of staging 18F-FDG PET/CT, beyond clinical risk factors, for predicting DM and OS in 176 patients after definitive chemoradiotherapy. Methods: The PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded. Univariate Cox regression was used to examine the prognostic value of these variables and clinical prognosticators for local treatment failure (LTF), OS, and DM. Multivariate analysis examined the effect of SUVmax, TLG, and MTV in the presence of other covariates. Kaplan–Meier curves were used to evaluate prognostic values of PET/CT parameters. Results: Primary tumors were distributed across all stages. Most patients underwent chemoradiotherapy only, and 11 also underwent tonsillectomy. On univariate analysis, primary tumor MTV was predictive of LTF (P = 0.005, hazard ratio [HR] = 2.4 for a doubling of MTV), DM and OS (P < 0.001 for both, HR = 1.9 and 1.8, respectively). The primary tumor TLG was associated with DM and OS (P < 0.001, HR = 1.6 and 1.7, respectively, for a doubling of TLG). The primary tumor SUVmax was associated with death (P = 0.029, HR = 1.1 for a 1-unit increase in standardized uptake value) but had no relationship with LTF or DM. In multivariate analysis, TLG and MTV remained associated with death after correcting for T stage (P = 0.0125 and 0.0324, respectively) whereas no relationship was seen between standardized uptake value and death after adjusting for T stage (P = 0.158). Conclusion: Parameters capturing the volume of 18F-FDG–positive disease (MTV or TLG) provide important prognostic information in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy and should be considered for risk stratification in this disease.

Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer

Traditionally, patients treated with chemoradiotherapy for node‐positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post‐treatment positron‐emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT‐based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity‐modulated radiation therapy and concurrent chemotherapy underwent post‐treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post‐treatment PET/CT. ND was reserved for patients with

Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

PURPOSE To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. METHODS AND MATERIALS Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. RESULTS Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). CONCLUSIONS Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses.

Bilateral implant reconstruction does not affect the quality of postmastectomy radiation therapy.

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.

Postmastectomy Radiation in Breast Cancer Patients With Pathologically Positive Lymph Nodes After Neoadjuvant Chemotherapy: Usage Rates and Survival Trends

PURPOSE To analyze postmastectomy radiation therapy (PMRT) usage and its association with overall survival (OS) in breast cancer patients with pathologically positive lymph nodes after neoadjuvant chemotherapy (NAC). METHODS AND MATERIALS Using the National Cancer Database, we identified women with nonmetastatic breast cancer diagnosed from 2004 to 2013 who had received NAC and undergone mastectomy with macroscopic pathologically positive lymph nodes. Joinpoint regression models were used to assess temporal trends in annual PMRT usage. Multivariable regression models were used to identify factors associated with PMRT use. A time-dependent Cox model was used to evaluate the predictors of mortality. RESULTS The study included 29,270 patients, of whom 62.5% received PMRT. PMRT was markedly underused among all nodal subgroups, in particular, among ypN2 (68.4%) and ypN3 (67.0%) patients. Hispanic patients and those with Medicaid or Medicare insurance were less likely to receive PMRT than were non-Hispanics and patients with other insurance carriers. The adjusted 5-year OS rates were similar in ypN1 and ypN2 patients with or without PMRT but were significantly greater in ypN3 patients receiving PMRT (66% vs 63%; P=.042). On multivariable analysis, PMRT was associated with improved survival only among ypN3 patients after adjusting for patient, facility, and tumor variables (multivariable hazard ratio 0.85; 95% confidence interval 0.74-0.97). CONCLUSIONS A considerable portion of breast cancer patients with advanced residual nodal disease after NAC did not receive appropriate adjuvant radiation. We also found socioeconomic disparities in national PMRT practice patterns. Patients with ypN3 disease might derive a survival benefit from PMRT.

Intracoronary brachytherapy for in-stent restenosis of drug-eluting stents

Purpose Given the limited salvage options for in-stent restenosis (ISR) of drug-eluting stents (DES), our high-volume cardiac catheterization laboratory has been performing intracoronary brachytherapy (ICBT) in patients with recurrent ISR of DES. This study analyzes their baseline characteristics and assesses the safety/toxicity of ICBT in this high-risk population. Methods and materials A retrospective analysis of patients treated with ICBT between September 2012 and December 2014 was performed. Patients with ISR twice in a single location were eligible. Procedural complications included vessel dissection, perforation, tamponade, slow/absent blood flow, and vessel closure. Postprocedural events included myocardial infarction, coronary artery bypass graft, congestive heart failure, stroke, bleeding, thrombosis, embolism, dissection, dialysis, or death occurring within 72 hours. A control group of patients with 2 episodes of ISR at 1 location who underwent percutaneous coronary intervention without ICBT was identified. Unpaired t tests and χ2 tests were used to compare the groups. Results There were 134 (78%) patients in the ICBT group with 141 treated lesions and 37 (22%) patients in the control group. There was a high prevalence of hyperlipidemia (>95%), hypertension (>95%), and diabetes (>50%) in both groups. The groups were well-balanced with respect to age, sex, and pre-existing medical conditions, with the exception of previous coronary artery bypass graft being more common the ICBT group. Procedural complication rates were low in the control and ICBT groups (0% vs 4.5%, P = .190). Postprocedural event rates were low (<5%) in both groups. Readmission rate at 30 days was 3.7% in the ICBT group and 5.4% in the control group (P = .649). Conclusions This is the largest recent known series looking at ICBT for recurrent ISR of DES. ICBT is a safe treatment option with similarly low rates (<5%) of procedural and postprocedural complications compared with percutaneous coronary intervention alone. This study establishes the safety of ICBT in a high-risk patient cohort.

Hypofractionated radiation treatment in the management of breast cancer

ABSTRACT Introduction: The standard treatment for early-stage breast cancer is breast conservation therapy, consisting of breast conserving surgery followed by adjuvant radiation treatment (RT). Conventionally-fractionated whole breast irradiation (CF-WBI) has been the standard RT regimen, but recently shorter courses of hypofractionated whole breast irradiation (HF-WBI) have been advocated for patient convenience and reduction in healthcare costs and resources. Areas covered: This review covers the major randomized European and Canadian trials comparing HF-WBI to CF-WBI with long-term follow-up, as well as additional recently closed randomized trials that further seek to define the applicability of HF-WBI in clinical practice. Randomized data is summarized in terms of clinical utility and for a variety of clinical applications. Recently published consensus guidelines and practical implementation of HF-WBI including its broader effect on the healthcare system are reviewed. Finally, an assessment of the emerging evidence in support of hypofractionation for locally advanced disease is presented. Expert commentary: HF-WBI has replaced CF-WBI as the accepted standard of care in most women with early-stage breast cancer who do not require regional nodal irradiation. Early data supports the continued study of hypofractionation in the locally advanced setting, however broad adoption awaits longer follow-up and additional data from ongoing clinical trials.

Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.

Trends and variations in postmastectomy radiation therapy for breast cancer in patients with 1 to 3 positive lymph nodes: A National Cancer Data Base analysis: PMRT in Patients With 1-3 + Lymph Nodes

High‐level evidence is lacking to guide treatment decisions about postmastectomy radiation therapy (PMRT) in patients who have breast cancer with 1 to 3 positive lymph nodes who receive contemporary systemic therapies, leading to potential variations in PMRT delivery. The objective of this study was to examine nationwide trends in PMRT use in this group.

The role of postmastectomy radiotherapy in patients with stage II breast cancer

Although the benefits of postmastectomy radiotherapy (PMRT) in patients with locally advanced breast cancer have been established in multiple randomized trials as well as the Early Breast Cancer Trialists’ Collaborative Group meta-analysis, the role of PMRT in patients with early-stage disease remains controversial. This article will discuss which patients with AJCC 7th edition stage II breast cancer may benefit from PMRT.