Smith Apisarnthanarax

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas

PURPOSE Uncontrolled local growth is the cause of death in ∼ 30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. METHODS The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. RESULTS Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6-53.8 and 34.9-52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. CONCLUSIONS Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons

PURPOSE Stereotactic body radiation therapy (SBRT) for treatment of liver tumors is often limited by liver dose constraints. Protons offer potential for more liver sparing, but clinical situations in which protons may be superior to photons are not well described. We developed and validated a treatment decision model to determine whether liver tumors of certain sizes and locations are more suited for photon versus proton SBRT. METHODS AND MATERIALS Six spherical mock tumors from 1 to 6 cm in diameter were contoured on computed tomography images of 1 patient at 4 locations: dome, caudal, left medial, and central. Photon and proton plans were generated to deliver 50 Gy in 5 fractions to each tumor and optimized to deliver equivalent target coverage and maximal liver sparing. Using these plans, we developed a hypothesis-generating model to predict the optimal modality for maximal liver sparing based on tumor size and location. We then validated this model in 10 patients with liver tumors. RESULTS Protons spared significantly more liver than photons for dome or central tumors ≥3 cm (dome: 134 ± 21 cm(3), P = .03; central: 108 ± 4 cm(3), P = .01). Our model correctly predicted the optimal SBRT modality for all 10 patients. For patients with dome or central tumors ≥3 cm, protons significantly increased the volume of liver spared (176 ± 21 cm(3), P = .01) and decreased the mean liver dose (8.4 vs 12.2 Gy, P = .01) while offering no significant advantage for tumors <3 cm at any location or for caudal and left medial tumors of any size. CONCLUSIONS When feasible, protons should be considered as the radiation modality of choice for dome and central tumors >3 cm to allow maximal liver sparing and potentially reduce radiation toxicity. Protons should also be considered for any tumor >5 cm if photon plans fail to achieve adequate coverage or exceed the mean liver threshold.

Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients

PURPOSE To evaluate the feasibility of a novel planning concept that differentially redistributes RT dose away from functional liver regions as defined by (99m)Tc-sulphur colloid (SC) uptake on patient SPECT/CT images. MATERIALS AND METHODS Ten HCC patients with different Child-Turcotte-Pugh scores (A5-B9) underwent SC SPECT/CT scans in treatment position prior to RT that were registered to planning CT scans. Proton pencil beam scanning (PBS) therapy plans were optimized to deliver 37.5-60.0Gy (RBE) over 5-15 fractions using single field uniform dose technique robust to range and setup uncertainty. Photon volumetrically modulated arc therapy (VMAT) plans were optimized to the same prescribed dose and minimum target coverage. For both treatment modalities, differential hepatic avoidance RT (DHART) plans were generated to decrease dose to functional liver volumes (FLV) defined by a range of thresholds relative to maximum SC uptake (43-90%) in the tumor-subtracted liver. Radiation dose was redistributed away from regions of increased SC uptake in each FLV by linearly scaling mean dose objectives during PBS or VMAT optimization. DHART planning feasibility was assessed by a significantly negative Spearmans rank correlation (RS) between dose difference and SC uptake. Patient, tumor, and treatment planning characteristics were tested for association to DHART planning feasibility using non-parametric Kruskal-Wallis ANOVA. RESULTS Compared to conventional plans, DHART plans achieved a 3% FLV dose reduction for every 10% SC uptake increase. DHART planning was feasible in the majority of patients with 60% of patients having RS<-0.5 (p<0.01, range -1.0 to 0.2) and was particularly effective in 30% of patients (RS<-0.9). Mean dose to FLV was reduced by up to 20% in these patients. Only fractionation regimen was associated with DHART planning feasibility: 15 fraction courses were more feasible than 5-6 fraction courses (RS<-0.93 vs. RS>-0.60, p<0.02). CONCLUSION Differential avoidance of functional liver regions defined on sulphur colloid SPECT/CT is achievable with either photon VMAT or proton PBS therapy. Further investigation with phantom studies and in a larger cohort of patients may validate the utility of DHART planning for HCC radiotherapy.

Clinical utility of integrated positron emission tomography/computed tomography imaging in the clinical management and radiation treatment planning of locally advanced rectal cancer

PURPOSE The role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in the staging and radiation treatment planning of locally advanced rectal cancer is ill defined. We studied the role of integrated PET/CT in the staging, radiation treatment planning, and use as an imaging biomarker in rectal cancer patients undergoing multimodality treatment. METHODS AND MATERIALS Thirty-four consecutive patients with T3-4N0-2M0-1 rectal adenocarcinoma underwent FDG-PET/CT scanning for staging and radiation treatment planning. Planned clinical management was compared before and after the addition of PET/CT information. Three radiation oncologists independently delineated CT-based gross tumor volumes (GTVCT) using clinical information and CT imaging data, as well as gradient autosegmented PET/CT-based GTVs (GTVPETCT). The mean GTV, interobserver concordance index (CCI), and proximal and distal margins were compared. The maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), and dual-time point PET parameters were correlated with clinicopathologic endpoints. RESULTS Clinical management was altered by PET/CT in 18% (n = 6) of patients with clinical upstaging in 6 patients and radiation treatment planning altered in 5 patients. Of the 30 evaluable preoperative patients, the mean GTVPETCT was significantly smaller than the mean GTVCT volumes: 88.1 versus 102.8 cc (P = .03). PET/CT significantly increased interobserver CCI in contouring GTV compared with CT only-based contouring: 0.56 versus 0.38 (P < .001). The proximal and distal margins were altered by a mean of 0.4 ± 0.24 cm and -0.25 ± 0.18 cm, respectively. MTV was inversely associated with 2-year progression-free survival (PFS) and overall survival (OS): smaller MTVs (<33 cc) had superior 2-year PFS (86% vs 60%, P = .04) and OS (100% vs 45%, P < .01) compared with larger MTVs (>33 cc). SUVmax and dual-time point PET parameters did not correlate with any endpoints. CONCLUSIONS FDG-PET/CT imaging impacts overall clinical management and is useful in the radiation treatment planning of rectal cancer patients by decreasing interobserver variability in contouring target boost volumes. Pretreatment MTV may provide useful prognostic information and requires further study.

Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience.

Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.

Proton beam therapy for hepatocellular carcinoma

ABSTRACT Introduction: Radiation therapy is an effective treatment option for hepatocellular carcinoma (HCC) patients. However, radiotherapy for HCC still has limited recognition as a standard treatment option in international consensus guidelines due to a paucity of randomized controlled trials and the risk of hepatotoxicity, which is primarily mediated by baseline liver function and dose delivered to non-tumor liver cells. Proton beam therapy (PBT) may offer advantages over photon-based radiation treatments through its dosimetric characteristic of sparing more liver volume at low to moderate doses. PBT has the potential to reduce radiation-related hepatotoxicity and allow for tumor dose escalation. Areas covered: This article reviews the clinical rationale for using PBT for HCC patients and clinical outcome and toxicity data from retrospective and prospective studies. PBT-specific technical challenges for these tumors and appropriate selection of patients to be treated with PBT are discussed. Expert commentary: Local control, overall survival, and toxicity results are promising for liver PBT. Future studies, including ongoing randomized cooperative group trials, will aim to determine the incremental benefit of PBT over photons and which patients are most suitable for PBT.

Assessment of functional liver reserve: old and new in 99mTc-sulfur colloid scintigraphy

Purpose A semiquantitative assessment of hepatic reticuloendothelial system function using colloidal particles scintigraphy has been proposed previously as a surrogate for liver function evaluation. In this article, we present an updated method for the overall assessment of technetium-99m (99mTc)-sulfur colloid (SC) biodistribution that combines information from planar and attenuation-corrected 99mTc-SC single-photon emission computed tomography (SPECT) images. The imaging protocol described here was developed as an easy-to-implement method to assess overall and regional liver function changes associated with chronic liver disease. Patients and methods Thirty patients with chronic liver disease and primary liver cancers underwent 99mTc-SC whole-body planar imaging and upper-abdomen SPECT/computed tomography (CT) imaging before external beam radiation therapy. Liver plus spleen and bone marrow counts as a fraction of whole-body total counts were calculated from SC planar imaging. Attenuation correction 99mTc-SC images were rigidly coregistered with treatment planning CT images that contained liver and spleen regions-of-interest. Ratios of total liver counts to total spleen counts were obtained from the aligned 99mTc-SC SPECT and CT images, and were subsequently used to separate liver plus spleen counts obtained on the planar images. This hybrid SPECT/CT and planar scintigraphy approach yielded an updated estimation of whole-body SC distribution. These biodistribution estimates were compared with historical data for reference. Statistical associations of 99mTc-SC biodistribution to liver function parameters and liver disease scoring systems (Child–Pugh) were evaluated by Spearman rank correlation. Results Percentages of 99mTc-SC uptake ranged from 19.3 to 77.3% for the liver; 3.4 to 40.7% for the spleen; and 19.0 to 56.7% for the bone marrow. Spearman’s correlation coefficient showed a significant statistical association between Child–Pugh score and bone marrow uptake at 0.55 (P⩽0.05), liver uptake at 0.71 (P⩽0.001), spleen uptake at 0.56 (P⩽0.05), and spleen plus bone marrow uptake at 0.71 (P⩽0.001). There was also a good correlation of SC uptake percentages with individual quantitative liver function components such as albumin and total bilirubin, and qualitative liver function components (varices, portal hypertension, ascites). For albumin: r=0.64 (P<0.001) compared with liver uptake percentage from the whole-body counts, r=0.49 (P<0.001) compared with splenic uptake percentage, and r=0.45 (P⩽0.05) compared with bone marrow uptake percentage. Conclusion We describe a novel liver function quantitative assessment method that combines whole-body planar images and SPECT/CT attenuation-corrected images of 99mTc-SC distribution. Attenuation-corrected SC images provide valuable regional liver function information, which is a unique feature compared with other imaging methods available. The results of our study indicate that the 99mTc-SC uptake by the liver, spleen, and bone marrow correlates with liver function parameters in patients with diffuse liver disease and the correlation with liver disease severity is slightly better for liver uptake percentages than for individual values of bone marrow and spleen uptake percentages.

Radiation recall myositis: Two sites, one patient

A 63 year-old-man presented to his physician with worsening left shoulder and left hip pain. Magnetic resonance imaging (MRI) of the shoulder was concerning for metastatic disease to the left acromion. Biopsy of this lesion revealed metastatic adenocarcinoma. Positron emission tomography and computed tomography revealed areas of increased fluorodeoxyglucose uptake in a large pancreatic tail lesion as well as in the thoracic spine, left lung, and left acetabulum. Fine needle aspiration of the pancreatic lesion showed 2 distinct tumor types: adenocarcinoma (TTF-1 negative) and neuroendocrine neoplasm. Further immunostains or tumor markers could not definitively identify the primary origin of the tumor. The patient was evaluated by oncology and was diagnosed with stage IV adenocarcinoma with neuroendocrine features of unknown primary (lung vs pancreas) with metastases to the thoracic spine, left acromion, and left acetabulum. Examination of the shoulder revealed fullness of the left acromion and tenderness on palpation. The left hip was uncomfortable although he could ambulate. His pain was managed adequately with multiple opioids. The left hip and left acromion were treated with palliative intent radiation therapy (RT) to 30 Gy in 10 daily

Functional imaging of radiation liver injury in a liver metastasis patient: imaging and pathologic correlation

BACKGROUND Radiation therapy (RT) is increasingly being utilized as a treatment modality for the treatment of primary and metastatic liver malignancies. Accurate assessment of liver function and prediction of radiation induced liver disease (RILD) remains a challenge with conventional laboratory tests and imaging. Imaging-pathology correlation of hepatic injury after RT has been described with computer tomography (CT) imaging that depicts perfusion changes. However, these imaging changes may not directly characterize the functional capacity of the liver. CASE PRESENTATION This case report describes a patient that received preoperative chemoradiation and surgical resection for a liver metastasis from endometrial cancer. Sulfur colloid (SC) single photon emission computed tomography (SPECT/CT) was obtained post-chemoradiation and prior to surgery. Imaging-pathology correlation between radiation changes depicted on functional imaging using SC SPECT/CT and corresponding histopathology is described. DISCUSSION Quantitative SC SPECT/CT may allow non-invasive assessment of global and spatial liver function before treatment and enable personalized treatment approaches for liver-directed therapies.

Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer

Background Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients. Methods An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses. Results Upfront proton treatment costs exceeded that of photons [