Manisha Palta

Stereotactic body radiotherapy: A critical review for nonradiation oncologists

Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease. Cancer 2014;120:942–954.

Human papillomavirus tumor infection in esophageal squamous cell carcinoma

The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status.

Hepatobiliary cancers, version 1.2017 featured updates to the NCCN guidelines

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

PURPOSE Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. METHODS AND MATERIALS Women aged ≥55 years with clinically node-negative, estrogen receptor-positive, and/or progesterone receptor-positive HER2-, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. RESULTS No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. CONCLUSIONS Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: changes in practice patterns after publication of Cancer and Leukemia Group B 9343.

The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged >70 years with clinical stage I (AJCC 7th edition), estrogen receptor‐positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study.

Investigation of sagittal image acquisition for 4D‐MRI with body area as respiratory surrogate

PURPOSE The authors have recently developed a novel 4D-MRI technique for imaging organ respiratory motion employing cine acquisition in the axial plane and using body area (BA) as a respiratory surrogate. A potential disadvantage associated with axial image acquisition is the space-dependent phase shift in the superior-inferior (SI) direction, i.e., different axial slice positions reach the respiratory peak at different respiratory phases. Since respiratory motion occurs mostly in the SI and anterior-posterior (AP) directions, sagittal image acquisition, which embeds motion information in these two directions, is expected to be more robust and less affected by phase-shift than axial image acquisition. This study aims to develop and evaluate a 4D-MRI technique using sagittal image acquisition. METHODS The authors evaluated axial BA and sagittal BA using both 4D-CT images (11 cancer patients) and cine MR images (6 healthy volunteers and 1 cancer patient) by comparing their corresponding space-dependent phase-shift in the SI direction (δSPS (SI)) and in the lateral direction (δSPS (LAT)), respectively. To evaluate sagittal BA 4D-MRI method, a motion phantom study and a digital phantom study were performed. Additionally, six patients who had cancer(s) in the liver were prospectively enrolled in this study. For each patient, multislice sagittal MR images were acquired for 4D-MRI reconstruction. 4D retrospective sorting was performed based on respiratory phases. Single-slice cine MRI was also acquired in the axial, coronal, and sagittal planes across the tumor center from which tumor motion trajectories in the SI, AP, and medial-lateral (ML) directions were extracted and used as references from comparison. All MR images were acquired in a 1.5 T scanner using a steady-state precession sequence (frame rate ∼ 3 frames/s). RESULTS 4D-CT scans showed that δSPS (SI) was significantly greater than δSPS (LAT) (p-value: 0.012); the median phase-shift was 16.9% and 7.7%, respectively. Body surface motion measurement from axial and sagittal MR cines also showed δSPS (SI) was significantly greater than δSPS (LAT). The median δSPS (SI) and δSPS (LAT) was 11.0% and 9.2% (p-value = 0.008), respectively. Tumor motion trajectories from 4D-MRI matched with those from single-slice cine MRI: the mean (±SD) absolute differences in tumor motion amplitude between the two were 1.5 ± 1.6 mm, 2.1 ± 1.9 mm, and 1.1 ± 1.0 mm in the SI, ML, and AP directions from this patient study. CONCLUSIONS Space-dependent phase shift is less problematic for sagittal acquisition than for axial acquisition. 4D-MRI using sagittal acquisition was successfully carried out in patients with hepatic tumors.

Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion

PURPOSE To evaluate the relationship between liver tumor motion and diaphragm motion. METHODS AND MATERIALS Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine-magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation-based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. RESULTS Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. CONCLUSIONS This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

Nonoperative management of rectal cancer.

Surgery has long been the primary curative modality for localized rectal cancer. Neoadjuvant chemoradiation has significantly improved local control rates and, in a significant minority, eradicated all disease. Patients who achieve a pathologic complete response to neoadjuvant therapy have an excellent prognosis, although the combination treatment is associated with long‐term morbidity. Because of this, a nonoperative management (NOM) strategy has been pursued to preserve sphincter function in select patients. Clinical and radiographic findings are used to identify patients achieving a clinical complete response to chemoradiation, and they are then followed with intensive surveillance. Incomplete, nonresponding and those demonstrating local progression are referred for salvage with standard surgery. Habr‐Gama and colleagues have published extensively on this treatment strategy and have laid the groundwork for this approach. This watch‐and‐wait strategy has evolved over time, and several groups have now reported their results, including recent prospective experiences. Although initial results appear promising, several significant challenges remain for NOM of rectal cancer. Further study is warranted before routine implementation in the clinic. Cancer 2016;122:34–41.

Preoperative chemoradiotherapy for locally advanced gastric cancer

BackgroundTo examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer.MethodsPatients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0.ResultsForty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively.ConclusionsPreoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

PURPOSE Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. METHODS AND MATERIALS From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. RESULTS Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). CONCLUSIONS The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.