Terence T. Sio

Comparing Gamma Knife and CyberKnife in patients with brain metastases

The authors compared the relative dosimetric merits of Gamma Knife (GK) and CyberKnife (CK) in 15 patients with 26 brain metastases. All patients were initially treated with the Leksell GK 4C. The same patients were used to generate comparative CK treatment plans. The tissue volume receiving more than 12 Gy (V12), the difference between V12 and tumor volume (V12net), homogeneity index (HI), and gradient indices (GI25, GI50) were calculated. Peripheral dose falloff and three conformity indices were compared. The median tumor volume was 2.50 cm3 (range, 0. 044‐19.9). A median dose of 18 Gy (range, 15‐22) was prescribed. In GK and CK plans, doses were prescribed to the 40‐50% and 77‐92% isodose lines, respectively. Comparing GK to CK, the respective parametric values (median±standard deviation) were: minimum dose (18.2±3.4 vs. 17.6±2.4 Gy, p=0.395); mean dose (29.6±5.1 vs.20.6±2.8 Gy, p<0.00001); maximum dose (40.3±6.5 vs.22.7±3.3 Gy, p<0.00001); and HI (2.22±0.19 vs. 1.18±0.06, p<0.00001). The median dosimetric indices (GK vs. CK, with range) were: RTOG_CI, 1.76 (1.12‐4.14) vs. 1.53 (1.16‐2.12), p=0.0220; CI, 1.76 (1.15‐4.14) vs. 1.55 (1.18‐2.21), p=0.050; nCI, 1.76 (1.59‐4.14) vs. 1.57 (1.20‐2.30), p=0.082; GI50, 2.91 (2.48‐3.67) vs. 4.90 (3.42‐11.68), p<0.00001; GI25, 6.58 (4.18‐10.20) vs. 14.85 (8.80‐48.37), p<0.00001. Average volume ratio (AVR) differences favored GK at multiple normalized isodose levels (p<0.00001). We concluded that in patients with brain metastases, CK and GK resulted in dosimetrically comparable plans that were nearly equivalent in several metrics, including target coverage and minimum dose within the target. Compared to GK, CK produced more homogenous plans with significantly lower mean and maximum doses, and achieved more conformal plans by RTOG_CI criteria. By GI and AVR analyses, GK plans had sharper peripheral dose falloff in most cases. PACS number: 89.20.‐a

Spot-scanned pancreatic stereotactic body proton therapy: A dosimetric feasibility and robustness study

PURPOSE We explored the dosimetric potential of spot-scanned stereotactic body proton therapy (SBPT) for pancreatic cancer. METHODS We compared SBPT to stereotactic body intensity-modulated radiotherapy (SB-IMRT) in 10 patients. We evaluated 3 variables in SBPT planning: (1) 4 and 6 mm spot size; (2) single vs. multi-field optimization (SFO vs. MFO); and (3) optimization target volume (OTV) expansion. Robustness analysis was performed with unidirectional isocenter shifts of ±3 mm in x, y, and z and ±3% stopping power uncertainties. RESULTS SBPT plans had lower V10Gy for the stomach and small and large bowels. Under static robustness, a 5 mm OTV and SFO-6 mm spot size represented the best compromise between target and normal structure. A 4-mm spot-size and 3 mm OTV resulted in significant target underdosing with deformable dose accumulation analysis. CONCLUSIONS This study provides a critical basis for clinical translation of spot size, optimization technique, and OTV expansion for pancreatic SBPT.

Prophylactic Cranial Irradiation for Extensive Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) has a high predilection for metastasizing to the brain after chemotherapy. This has been blamed on the blood-brain barrier, which prevents chemotherapy from penetrating into the brain, thus creating a sanctuary site. It has been estimated that up to three quarters of patients with SCLC will eventually develop brain metastases. This led investigators to administer prophylactic cranial irradiation (PCI) to decrease this risk. Several trials were performed in patients with SCLC after initial therapy (chemotherapy with or without thoracic radiotherapy) that compared the outcomes of PCI versus no PCI. Early trials generally found that PCI significantly decreased the risk of brain metastases but did not significantly improve survival. These trials were re-evaluated in two larger meta-analyses that included patients with either limited-stage SCLC or extensive-stage SCLC (ESCLC). Both meta-analyses reported that PCI significantly decreased brain metastases and improved survival in patients who had a complete response following initial therapy. These studies were performed before the advent of modern imaging with computed tomography or magnetic resonance imaging (MRI). There have been two modern trials of PCI versus no PCI in patients with ESCLC and both found that PCI decreases brain metastases. The first did not include brain MRI before registration and found that PCI improved survival, whereas the second study did include MRI before registration and at frequent intervals thereafter. That trial found that PCI did not confer a survival advantage. This review will examine the evidence and provide recommendations regarding the role of PCI for patients with ESCLC.

Long-term treatment outcomes for locally advanced esophageal cancer: A single-institution experience

Objectives:To determine long-term outcomes in patients with locally advanced esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT] and surgery, TMT) or definitive CRT. Methods:We retrospectively identified patients with advanced esophageal carcinoma treated with curative intent at our institution between 1998 and 2004. Identified patients were separated into 3 groups: patients who received TMT, patients who received CRT, and patients who began treatment with trimodality intent but did not undergo surgery (PTMT). Local control, overall survival (OS), and distant metastasis-free survival were compared using Kaplan-Meier statistics. Results:Among the 265 patients included, median follow-up was 6.4 years for surviving patients and 1.7 years for all patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169 patients (64%) completing TMT, 46 patients medically unable to undergo surgery after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was 20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT group had the highest 5- and 10-year OS (32% and 19%, respectively). Local control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%, respectively. By treatment modality, 5-year local control was best (82%) for TMT, compared with 60% for CRT and 40% for PTMT groups (P<0.001). Conclusions:Patients who completed TMT had the best local control and long-term OS. In the context of TMT, surgery seemed more beneficial in patients with esophageal adenocarcinoma versus squamous cell carcinoma.

Percutaneous revascularization in patients treated with thoracic radiation for cancer

Objectives To assess coronary revascularization outcomes in patients with previous thoracic radiation therapy (XRT). Background Previous chest radiation has been reported to adversely affect long term survival in patients with coronary disease treated with percutaneous coronary interventions (PCI). Methods Retrospective, single center cohort study of patients previously treated with thoracic radiation and PCI. Patients were propensity matched against control patients without radiation undergoing revascularization during the same time period. Results We identified 116 patients with radiation followed by PCI (XRT‐PCI group) and 408 controls. Acute procedural complications were similar between groups. There were no differences in all‐cause and cardiac mortality between groups (all‐cause mortality HR 1.31, P = .078; cardiac mortality 0.78, P = .49). Conclusion Patients with prior thoracic radiation and coronary disease treated with PCI have similar procedural complications and long term mortality when compared to control subjects.

Outcome of Transplant-fallout Patients With Unresectable Cholangiocarcinoma.

Objectives:The aim of this was to determine survival after starting neoadjuvant therapy for patients who became ineligible for orthotopic liver transplantation (OLT). Methods and Materials:Since January 1993, 215 patients with unresectable cholangiocarcinoma began treatment with planned OLT. Treatment included external-beam radiation therapy (EBRT) with fluorouracil, bile duct brachytherapy, and postradiotherapy fluorouracil or capecitabine before OLT. Adverse findings at the staging operation, death, and other factors precluded OLT in 63 patients (29%), of whom 61 completed neoadjuvant chemoradiation. Results:By October 2012, 56 (89%) of the 63 patients unable to undergo OLT had died. Twenty-two patients (35%) became ineligible for OLT before the staging operation, 38 (60%) at the staging operation, and 3 (5%) after staging. From the date of diagnosis, median overall survival was 12.3 months. Survival was 17% at 18 months and 7% at 24 months. Median survival after fallout was 6.8 months. Median survival after the staging operation was 6 months. Two patients lived for 3.7 and 8.7 years before dying of cancer or liver failure caused by persistent biliary stricture at the site of the original cancer, respectively. Univariate analysis showed that time from diagnosis to fallout correlated with overall survival (P=0.04). Conclusions:In highly selected patients initially suitable for OLT, the mortality rate for cholangiocarcinoma was high in patients who became ineligible for OLT. Their survival, however, was comparable to expected survival for patients with locally advanced or metastatic disease treated with nontransplant therapies. The most common reason for patient fallout was adverse findings at the staging operation.

Adaptation of the Stanford technique for treatment of bulky cutaneous T-cell lymphoma of the head

Electron beam radiation therapy is an effective treatment for cutaneous T-cell lymphoma (CTCL).1,2 The first description of total skin electron therapy came from Stanford University.1,3 Prolonged treatment to ≥3000 cGy in 6 to 7 weeks is not feasible for many patients in a palliative setting. Hypofractionated regimens are associated with high response rates.4-8 We describe a case of bulky CTCL of the head treated with a unique adaptation of the Stanford technique.

The impact of CyberKnife's prescription isodose percentage on intracranial target planning

To the Editor: Recently, a detailed comparative study regarding intracranial Gamma Knife (GK) vs. CyberKnife (CK) intracranial dosimetry has been published by your Journal.(1) In a group of 15 patients with 26 brain metastases, we showed that CK produced more homogeneous and conformal plans, while the GK plans had sharper peripheral dose falloff in most cases. In the CK plans, by convention, the applied range of prescription isodose percentage (PIP) was 77%–92%, with a median value of 86%. Intrigued by the results, we hypothesized that lowering the PIP in CK planning would improve peripheral dose falloff, without compromising the excellent dosimetric conformality which had previously been achieved. Secondarily, it was expected that, as PIP decreased, the stereotactic radiosurgical (SRS) plans would become less homogeneous as maximum dose within the target increased. We thank you for the opportunity to share with you the additional results that were generated from this investigation. Parts of the methods and materials have been previously described.(1) We compared the relative dosimetric merit of various prescription isodose levels in CK’s MultiPlan (Accuray Inc, Sunnyvale, CA). The same 15-patient series was used for dosimetric planning. For each tumor, the PIP was varied at three levels averaging approximately 50, 65, and 85% (CK50, CK65 and CK85; Table 1). The homogeneity (HI) and gradient (GI) indices, modified conformity index (mCI, the ratio of the prescription isodose volume to the tumor volume receiving at least the prescription dose), and an MPS-defined quantity called “new CI” (nCI, the ratio of mCI to target coverage, also the inverse of van’t Riet’s Conformation Number) were computed. For peripheral dose falloff, GI50 was calculated as the ratio of the volume enclosed by the isodose at 50% of the prescription dose level to the volume enclosed by the original prescription isodose. GI25, GI40, GI60, and GI80 were calculated in a similar manner. Statistical analyses were performed using analysis of variance (ANOVA) and nonparametric Kruskal-Wallis tests. We found that the mean tumor volume was 4.4 cm3; a median dose of 18 Gy was prescribed. For CK50, CK65, and CK85 series, the coverage was maintained at 96%–100% in all cases. Optimized plans in each scenario across various PIPs were computed, and dosimetric constraints of critical organ structures were all met. Minimum, average, maximum doses, HI, nCI, GI25, GI50, and MU were reported (Table 2). Comparing across the CK50, CK65, and CK85 series, the median mCIs were: 1.48, 1.36, and 1.52, p =.086, respectively. The remaining gradient indices were: GI40 (5.8, 6.9, and 7.6, p = 0.0008); for GI60 (2.8, 3.4, and 3.8), GI80 (1.6, 1.9, and 2.2), and GI90 (1.3, 1.4, and 1.6), p < 0.00001 in all cases. In our study, as expected, the selection of a PIP had a statistically significant impact on HI, mean, and maximum doses. By both mCI and nCI, CK65 produced the most conformal plans which nearly reached statistical significance. Importantly, CK50 had significantly sharpest dose falloff at all gradient index levels, with the exception of GI25. However, dosimetric plans prescribing to CK50 required significantly longer treatment times by MU estimation. In current clinical practices, deciding a prescription isodose level in CK varies by individual plan and preference, and clearly no consensus exists. The CK is a relatively new modality for SRS, which is stereotactically capable for extracranial indications, as well. For GK and linacbased intracranial SRS, it is common to prescribe to 40%–60% and 80%–95% of PIP, respectively. It is then customarily believed that the PIPs of CK should fall between those of the GK and linac-based SRS plans, as CK shares features of both. For CK dosimetric planning, some JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, VOLUME 15, NUMBER 5, 2014

Dosimetric Correlate of Cardiac-Specific Survival Among Patients Undergoing Coronary Artery Stenting After Thoracic Radiotherapy For Cancer.

Objectives: To retrospectively evaluate outcomes among cancer survivors previously treated with thoracic radiotherapy (RT) who later underwent percutaneous coronary intervention (PCI). Methods: From 1998 to 2012, 76 patients first received curative RT (>30 Gy, except for Hodgkin lymphoma patients) involving the heart and lungs followed by PCI. Heart and lung–specific dosimetric parameters were correlated with overall survival (OS) and cardiac-specific survival by Cox variate methods. Results: The mean interval between cancer diagnosis and PCI was 3.7 years (range, 0.1 to 12.6 y). Median follow-up since cancer diagnosis was 5.5 years. At analysis, 46 patients (61%) were alive, 5 (7%) died of cardiac causes, and 9 (12%) of cancer. Higher maximum RT heart dose was related to poorer OS since PCI (P=0.009). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (P=0.005) and higher mean heart dose (P<0.001) were related to poorer OS since cancer diagnosis. &bgr;-Blockers, higher mean heart dose (hazard ratio [HR]=1.49, P<0.001), and percentage of targeted volume or organ receiving ≥40 Gy for heart doses (HR=1.32, P<0.001) were associated with poorer non–cancer-specific survival since cancer diagnosis. Diabetes (HR=3.84, P=0.008) and increased percentage of targeted volume or organ receiving ≥45 Gy (HR=1.01 per additional 100 cm3 irradiated, P=0.01) for the heart decreased major adverse cardiac event–free survival. Conclusions: Prior heart and lung–directed RT had volume-dependent and dose-dependent adverse effects on long-term cardiac outcomes for patients subsequently treated with PCI. RT planning that minimizes heart and lung irradiation doses should be encouraged.

Angiosarcoma of the seminal vesicle: a case report of long-term survival following multimodality therapy.

Angiosarcoma of the seminal vesicle is an extremely rare malignancy, with few published case reports in the literature. We present a case of primary angiosarcoma of the seminal vesicle in a 45-year-old male who was treated with multimodality therapy, consisting of neoadjuvant chemotherapy and chemoradiation followed by surgical resection and intraoperative radiation therapy. He has been free of cancer recurrence for more than six years after completion of therapy. To our knowledge, this represents the longest reported survival of a patient with this rare tumor, and one of the few cases reported using a multimodality therapy approach.