Shalini Moningi

Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer

PURPOSE Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. RESULTS Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm(3)) than in CRT (344.6 cm(3); P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm(3) vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002). CONCLUSIONS SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted.

Stereotactic body radiation therapy in pancreatic cancer: the new frontier.

Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3–5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.

Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

PURPOSE Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. METHODS AND MATERIALS An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. RESULTS Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. CONCLUSION Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy may enhance tumor control with an acceptably low risk of long-term sequelae in this sensitive patient population.

Correlation of Clinical Stage and Performance Status With Quality of Life in Patients Seen in a Pancreas Multidisciplinary Clinic

INTRODUCTION The objectives of this study were to evaluate quality of life (QoL) in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC), and to examine associations between disease status, performance status, and QoL in order to identify patient subgroups that are most at risk for reduced QoL. PATIENTS AND METHODS Data from 77 patients were evaluated. At initial presentation, disease and performance status were assessed, as well as QoL, which was obtained with the European Organisation for Research and Treatment of Cancer QLQ-PAN26 questionnaire. Statistical analyses examined associations between QoL, disease status, and performance status. RESULTS Digestive symptoms (P < .003) significantly differed by pancreatic disease status (resectable, resected, locally advanced, and metastatic). Patients with a worse performance status, defined as Eastern Cooperative Oncology Group ≥ 1, were more likely to report symptomatic pancreatic pain (P = .001), digestive symptoms (P = .017), cachexia (P = .004), and ascites (P < .001) compared with patients with a performance status of 0. The majority (92%) of patients reported a significant fear of future health problems, regardless of disease status or performance status. CONCLUSION Although several measures of QoL have been observed in all patients, certain measures appear to correlate specifically with worse disease status. Therefore, routine assessment of QoL is suggested in order to guide treatment decisions. Further investigation on optimizing the use of QoL measures and patient-reported outcomes to better tailor management is warranted.

Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas

BACKGROUND Pancreatic adenosquamous carcinoma (PASC) accounts for only 1-4% of all exocrine pancreatic cancers and carries a particularly poor prognosis. This retrospective study was performed to determine whether inclusion of a platinum agent as part of adjuvant therapy is associated with improved survival in patients with resected PASC. METHODS Records of all patients who underwent pancreatic resection at Johns Hopkins Hospital from 1986 to 2012 were reviewed to identify those with PASC. Multivariable Cox proportional hazards modeling was used to assess for significant associations between patient characteristics and survival. RESULTS In total, 62 patients (1.1%) with resected PASC were identified among 5,627 cases. Median age was 68 [interquartile range (IQR), 57-77] and 44% were female. Multivariate analysis revealed that, among all patients (n=62), the following factors were independently predictive of poor survival: lack of adjuvant therapy [hazard ratio (HR) =3.6; 95% confidence interval (CI), 1.8-7.0; P<0.001], margin-positive resection (HR =3.5; 95% CI, 1.8-6.8; P<0.001), lymph node involvement (HR =3.5; 95% CI, 1.5-8.2; P=0.004), and age (HR =1.0; 95% CI, 1.0-1.1; P=0.035). There were no significant differences between patients who did and did not receive adjuvant therapy following resection (all P>0.05). A second multivariable model included only those patients who received adjuvant therapy (n=39). Lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.4; 95% CI, 1.0-5.8; P=0.040) and larger tumor diameter (HR =1.3; 95% CI, 1.0-1.6; P=0.047) were independent predictors of inferior survival. CONCLUSIONS Addition of a platinum agent to adjuvant regimens for resected PASC may improve survival among these high-risk patients, though collaborative prospective investigation is needed.

High-dose-rate intraoperative radiation therapy: The nuts and bolts of starting a program

High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach. Proper administration of HDR-IORT requires institutional support and a joint effort among physics staff, oncologists, surgeons, anesthesiologists, and nurses. In order to determine the true efficacy of IORT for various malignancies, collaboration among institutions with established IORT programs is needed.

Analysis of fiducials implanted during EUS for patients with localized rectal cancer receiving high-dose rate endorectal brachytherapy

Colorectal cancer is the third most common malignancy and the third leading cause of cancer-related death in the United States, with more than 40,000 rectal cancer cases diagnosed each year.1 Standard treatment for localized (ie, resectable) rectal cancer includes 5-fluorouracil (5-FU)-based chemoradiation therapy followed by surgery. Improved radiation technology including image-guided radiation therapy (RT) and brachytherapy (contact therapy) can allow for the delivery of higher doses of RT to the rectal tumor over a shorter time period. These treatments may result in improved outcomes; however, they require fiducial markers to allow better localization and targeting of the rectal tumor. In this retrospective study, we evaluated the role of gold fiducial markers in patients receiving neoadjuvant endorectal brachytherapy in patients with localized rectal tumors.

Analysis of fiducials implanted during endoscopic ultrasound (EUS) for locally advanced rectal cancer patients receiving high-dose rate endorectal brachytherapy (Endo-HDR).

655 Background: Rectal cancer affects over 40,000 patients in the US per year. The current standard of care for patients with localized rectal cancer is neoadjuvant radiation therapy with concurrent chemotherapy (NCRT) followed by surgery; however, it has shown no proven survival benefit for locally advanced rectal cancer patients. Preliminary results show that a short course of radiation therapy, using high-dose rate endorectal brachytherapy (Endo-HDR), may be as effective with less toxicity and delay to time of surgery. This requires the placement of fiducial markers, using an endoscopic ultrasound guided method (EUS), into the tumor for accurate source placement and treatment. Our aim is to compare three different types of fiducials in terms of visibility and migration. Methods: 12 patients with locally advanced rectal cancer that received Endo-HDR and EUS guided fiducial placement were retrospectively evaluated at JHH. Results: 12 patients underwent EUS guided placement of 42 fiducials. For 11 of our ...

Effects of gemcitabine and stereotactic body radiotherapy on quality of life in locally advanced pancreatic cancer.

278 Background: Existing literature on the impact of radiation therapy for locally advanced pancreatic cancer (LAPC) on quality of life (QoL) is limited and is specific to standard chemoradiation. We prospectively investigated patient-reported QoL after treatment with fractionated stereotactic body radiation therapy (SBRT). Methods: Forty-nine patients with LAPC treated were prospectively enrolled in a clinical trial at 3 institutions. Participants received a total of 33 Gy in 6.6 Gy daily fractions using SBRT either upfront (N=5) or after a single induction cycle of gemcitabine (N=44), followed by post-SBRT gemcitabine until evidence of disease progression. Two validated questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and pancreatic cancer-specific QLQ-PAN26, were administered to patients prior to SBRT and at 4-weeks and 3 to 4-months following SBRT. Results: QoL questionnaires were available for 43 patients (88%) in the clinical trial at enrollment, of whic...