The role of a radiopaque peri-rectal hydrogel spacer in aiding accurate daily image-guidance for prostate stereotactic radiotherapy.

Introduction: Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer. Materials and methods: Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared. Results: 140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators. Conclusions: For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.

SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. METHODS: 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. DISCUSSION: This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. TRIAL REGISTRATION: This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Major Complications and Adverse Events Related to Use of SpaceOAR Hydrogel for Prostate Cancer Radiotherapy.

OBJECTIVE: To determine the prevalence and severity of SpaceOAR-related adverse events using the Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: We analyzed SpaceOAR-related adverse event reports in the Manufacturer and User Facility Device Experience (MAUDE) database from January 2015 to May 2023. For each report, the event type, associated device and patient problems, event description, event timing, and event severity stratified by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE) grading system were recorded. RESULTS: From 2015 to 2022, 206,619 SpaceOAR devices were sold. From January 2015 to May 2023, we identified 981 reports describing 990 SpaceOAR-related adverse events. Malfunctions were the most common event type (N = 626), followed by patient injuries (N = 350) with few reported deaths (N = 5). Device positioning problems were the most frequent device issue (N = 686). Pain was the most reported patient problem (N = 216). Abscesses and fistulas related to the device were each reported in 91 events. A noteworthy portion of relevant adverse events occurred before the initiation of radiation (N = 35, 22.4%), suggesting the device, rather than the radiation, was responsible. In total, 470 (50.2%) and 344 (36.7%) of the adverse events were CTCAE grade 1 and 2, respectively. There were 123 (13.1%) events that were CTCAE grade ≥3. CONCLUSION: We identified multiple reports of SpaceOAR-related adverse events, many of which are more serious than have been reported in clinical trials. While SpaceOAR use is common, suggesting these events are rare, these data highlight the need for continued postmarket surveillance.

Same-day versus delayed simulation imaging after placement of a perirectal hydrogel spacer for prostate radiotherapy.

Introduction: Placement of a perirectal hydrogel spacer has been demonstrated to reduce the risk of rectal toxicity from prostate radiation. Practices vary regarding the timing of CT simulation after hydrogel placement, and the ideal schedule remains unknown. Methods: Thirty patients with localized prostate adenocarcinoma underwent transrectal ultrasound-guided placement of an iodinated SpaceOAR™ hydrogel prior to radiotherapy. Per evolving practice, 15 completed same-day simulation and 15 returned for simulation 1-2 weeks later. Hydrogel volume, perirectal distance, air-void volume, and rectal dosimetry per NRG GU005 were compared between CT simulation, 1st fraction Cone-Beam-CT (CBCT), and final CBCT. Results: CT simulation occurred 8.8 ± 2.4 days after placement in the delayed group, with no significant difference in the interval between simulation and 1st fraction between groups (p = 0.165). Greater observed de-creases in hydrogel volume (0.57 cc vs. 0.04 cc, p = 0.0002), and perirectal distance at both mid-gland (1.32 mm vs. 0.17 mm) and tallest point (2.40 mm vs. 0.04 mm) were seen on 1st-fraction CBCT in the same-day group (p = 0.0039; p = 0.0002). Per dosimetry recalculated on 1st fraction CBCT, five (D3 cc and D50%) versus one (D50%) rectal dose parameters were exceeded in the same-day and delayed groups, respectively, and 10 versus one parameters had a relative increase of ≥ 20%. Conclusion: Due to the evolving anatomic changes in the days following hydrogel placement, same-day simulation scanning may introduce unintended variability in rectal dosimetry at the time of prostate radiotherapy.

The effect of gastric fundus radiation dose on postoperative anastomotic leakage in esophageal cancer.

Introduction: Standard-of-care treatment for locally advanced esophageal carcinoma (LAEC) includes neoadjuvant chemoradiotherapy followed by esophagectomy. A potentially catastrophic surgical complication is the development of a postoperative anastomotic leak. To date, the association with radiation dose exposure had been inconclusive. We examined the correlation between radiation exposure to the gastric fundus and risk of postoperative leakage using contemporary radiation doses and fractionation. Methods: A total of 69 consecutive patients with LAEC who underwent neoadjuvant chemoradiotherapy followed by esophagectomy in our tertiary center were prospectively followed (median, 27 months). Neoadjuvant regimen included 50.4 Gy in 28 fractions with 5-fluorouracil and cisplatin and 41.4 Gy in 23 fractions with carboplatin and paclitaxel. The gastric fundus was contoured and dosimetric and radiation technique parameters were retrospectively evaluated. Results: Of the total number of patients, 71% and 29% had esophageal and gastroesophageal junction (GEJ) tumors, respectively. Fourteen patients (20.3%) experienced anastomotic leaks within a median of 2 days postoperatively, 78.6% of whom had lower third esophagus or GEJ primaries. Mean and minimum fundus dose did not significantly differ between those with and those without leakage (p = 0.42, p = 0.51). Mean fundus V25, V30, and V35 doses were numerically but not statistically higher in those with anastomotic leak (p = 0.58, p = 0.39, and p = 0.30, respectively). No correlation with incidence of leakage was seen between 3D and IMRT treatment modalities. Conclusions: In our comparatively large prospectively collected series of patients treated for LAEC, radiation dose to the gastric fundus during neoadjuvant combination therapy prior to surgery did not correlate with the risk of postoperative anastomotic leak.

Dehydration Reduction in Head and Neck Cancer (DRIHNC) Trial: Daily Oral Fluid and Electrolyte Maintenance to Prevent Acute Care Clinic and Emergency Department Visits for Patients Receiving Radiation for Head and Neck and Esophageal Cancer.

Purpose: Patients with head and neck (H&N) and esophageal cancer are at high risk for treatment-related symptomatic dehydration, often leading to interventions and hospital admissions. We tested the hypothesis that preemptive daily oral hydration during curative-intent radiation therapy would decrease dehydration as measured by intravenous fluid (IVF) delivery, acute care clinic (ACC) visits, and emergency department (ED) presentations. Methods and Materials: Patients with H&N or esophageal cancer undergoing definitive radiation therapy were enrolled in this prospective pilot study. Beyond standard nutritional counseling, patients were given one 20-oz bottle of an electrolyte-infused solution (EIS) daily throughout treatment. Compliance, presentations to the hospital ACC and/or ED for dehydration-related indications, and IVF infusions were documented and compared with a matched contemporary control cohort. The incidence and frequency of outcomes were compared with the Fisher exact test and Wilcoxon rank-sum test, respectively. Results: Thirty-one patients were compared during a 6-month period. Mean and median compliance rates were 87.4% and 100%, respectively. There were 0 unplanned dehydration-related ED presentations in the study group versus 3 (9.7%) among controls (P = .08). Of patients in the intervention cohort, 32.3% required presentation to the ACC, versus 64.5% in the control cohort (P = .02), with a total of 26 versus 117 visits, respectively (P = .002). On multivariable analysis, receipt of the EIS in the intervention cohort was the only significantly associated factor (P = .02). Among patients in the intervention cohort, 35.5% required IVF during treatment, versus 64.5% among controls (P = .004). The difference in ACC visits (P = .003) and IVF received (P = .008) was especially notable among patients with esophageal cancer. Patients with ≥60% EIS compliance had slightly fewer ACC visits versus those with <60% compliance (P = .067). Conclusions: Regimented oral hydration during radiation for H&N and esophageal cancer was associated with a significant decrease in ACC visits and IVF delivery during definitive radiation therapy. This noninvasive and inexpensive preventative program in a high-risk cohort warrants further study.

Monte Carlo Dose Calculation Using MRI Based Synthetic CT Generated by Fully Convolutional Neural Network for Gamma Knife Radiosurgery.

The aim of this work is to study the dosimetric effect from generated synthetic computed tomography (sCT) from magnetic resonance (MR) images using a deep learning algorithm for Gamma Knife (GK) stereotactic radiosurgery (SRS). The Monte Carlo (MC) method is used for dose calculations. Thirty patients were retrospectively selected with our institution IRB's approval. All patients were treated with GK SRS based on T1-weighted MR images and also underwent conventional external beam treatment with a CT scan. Image datasets were preprocessed with registration and were normalized to obtain similar intensity for the pairs of MR and CT images. A deep convolutional neural network arranged in an encoder-decoder fashion was used to learn the direct mapping from MR to the corresponding CT. A number of metrics including the voxel-wise mean error (ME) and mean absolute error (MAE) were used for evaluating the difference between generated sCT and the true CT. To study the dosimetric accuracy, MC simulations were performed based on the true CT and sCT using the same treatment parameters. The method produced an MAE of 86.6 ± 34.1 Hundsfield units (HU) and a mean squared error (MSE) of 160.9 ± 32.8. The mean Dice similarity coefficient was 0.82 ± 0.05 for HU > 200. The difference for dose-volume parameter D95 between the ground true dose and the dose calculated with sCT was 1.1% if a synthetic CT-to-density table was used, and 4.9% compared with the calculations based on the water-brain phantom.

Focal Prostate Stereotactic Body Radiation Therapy With Correlative Pathological and Radiographic-Based Treatment Planning.

INTRODUCTION: Advances in multiparametric MRI (mpMRI) combining anatomic and functional imaging can accurately identify foci of adenocarcinoma within the prostate, offering the possibility of partial gland therapy. We performed tandem prospective pilot trials to investigate the feasibility of focal prostate SBRT (f-SBRT) based on correlating diagnostic mpMRI and biopsies with confirmatory pathology in treatment planning. MATERIALS AND METHODS: Patients with pathologic focal Gleason 6-7 disease and a corresponding PIRADS 4-5 lesion on mpMRI underwent targeted and comprehensive biopsies using MRI/ultrasound fusion under electromagnetic sensor navigation. After rigorous analysis for imaging biopsy concordance, five of 18 patients were eligible to proceed to f-SBRT. Chi-squared test was used for differences from expected outcomes, and concordance was estimated with binomial distribution theory and Wilson's method. RESULTS: Six patients had Gleason 6 and 12 had Gleason 3 + 4 disease (mean PSA: 5.8 ng/ml, range: 2.2-8.4). Absolute concordance was 43.8% (95% CI: 0.20, 0.64). Patterns of discordance included additional sites of ipsilateral disease, bilateral disease, and negative target. Five were upstaged to a new NCCN risk category necessitating treatment escalation. The five patients with concordant pathology completed three-fraction f-SBRT with sparing of the surrounding normal structures (including contralateral neurovascular bundle), with no reported grade 2+ toxicities and favorable PSA responses (mean: 41% decrease). CONCLUSIONS: On our pilot trials of f-SBRT planning using rigorous imaging and pathology concordance, image-guided confirmatory biopsies frequently revealed additional disease, suggesting the need for caution in partial-gland therapy. For truly focal disease, f-SBRT provided excellent dosimetry, minimal toxicity, and encouraging biochemical response. Clinical Trial Registration: www.clinicaltrials.gov, NCT02681614; NCT02163317.

Synthetic CT Generation of the Pelvis in Patients With Cervical Cancer: A Single Input Approach Using Generative Adversarial Network.

Multi-modality imaging constitutes a foundation of precision medicine, especially in oncology where reliable and rapid imaging techniques are needed in order to insure adequate diagnosis and treatment. In cervical cancer, precision oncology requires the acquisition of 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance (MR), and computed tomography (CT) images. Thereafter, images are co-registered to derive electron density attributes required for FDG-PET attenuation correction and radiation therapy planning. Nevertheless, this traditional approach is subject to MR-CT registration defects, expands treatment expenses, and increases the patient's radiation exposure. To overcome these disadvantages, we propose a new framework for cross-modality image synthesis which we apply on MR-CT image translation for cervical cancer diagnosis and treatment. The framework is based on a conditional generative adversarial network (cGAN) and illustrates a novel tactic that addresses, simplistically but efficiently, the paradigm of vanishing gradient vs. feature extraction in deep learning. Its contributions are summarized as follows: 1) The approach -termed sU-cGAN-uses, for the first time, a shallow U-Net (sU-Net) with an encoder/decoder depth of 2 as generator; 2) sU-cGAN's input is the same MR sequence that is used for radiological diagnosis, i.e. T2-weighted, Turbo Spin Echo Single Shot (TSE-SSH) MR images; 3) Despite limited training data and a single input channel approach, sU-cGAN outperforms other state of the art deep learning methods and enables accurate synthetic CT (sCT) generation. In conclusion, the suggested framework should be studied further in the clinical settings. Moreover, the sU-Net model is worth exploring in other computer vision tasks.

Case Report: Role of an Iodinated Rectal Hydrogel Spacer, SpaceOAR Vue™, in the Context of Low-Dose-Rate Prostate Brachytherapy, for Enhanced Post-Operative Contouring to Aid in Accurate Implant Evaluation and Dosimetry.

We present a case series of 13 consecutive patients with prostate cancer treated with low-dose-rate (LDR) brachytherapy, utilizing SpaceOAR Vue™, the recent iodinated iteration of the SpaceOAR™ hydrogel rectal spacer. Low- and favorable intermediate-risk patients receiving monotherapy and unfavorable intermediate- and high-risk patients undergoing a brachytherapy boost were included. Permanent brachytherapy can result in subacute and late rectal toxicity, and precise contouring of the anterior rectal wall and posterior aspect of the prostate is essential for accurate dosimetry to confirm a safe implant. Clearly visible on non-contrast CT imaging, SpaceOAR Vue™ can substantially aid in post-implant contouring and analysis. Not previously described in the literature in the context of LDR brachytherapy, we demonstrate the added clinical benefit of placing a well-visualized rectal spacer.

Appropriate Methodology for EBRT and HDR Intracavitary/Interstitial Brachytherapy Dose Composite and Clinical Plan Evaluation for Patients With Cervical Cancer.

PURPOSE: This study assessed the appropriateness of full parameter addition (FPA) methods with respect to the 3-dimensional deformable dose composite method for evaluating combined external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: A total of 22 patients who received EBRT and high-dose-rate ICBT were retrospectively evaluated. Split-ring and tandem applicators were used for all patients. Additional interstitial needles were used for 5 patients to supplement the implant. Deformable image registrations were performed to deform the secondary EBRT and ICBT planning computed tomography (CT) images onto the reference CT from the third fraction of ICBT. The Dice similarity coefficient was used to evaluate the quality of deformable registration. Doses were transferred to the reference CT, scaled to the equivalent dose in 2-Gy fractions and combined to create the dose composite. Eight dose-accumulation methods were evaluated and compared. D2cc and D0.1cc for organs at risk were investigated. RESULTS: The differences in D2cc for rectum, bladder, sigmoid, and bowel between the FPA method for whole-pelvis EBRT and ICBT, calculated using an old American Brachytherapy Society worksheet (FPA_Eh + I_old) and deformable composite for EBRT with boosts and ICBT (Def_E + B + I) were -2.19 ± 1.37 Gyα/ß = 3, -0.64 ± 1.13 Gyα/ß = 3, -2.06 ± 2.71 Gyα/ß = 3, and -1.59 ± 0.89 Gyα/ß = 3, respectively. The differences in D2cc for rectum, bladder, sigmoid, and bowel between the new ABS worksheet (FPA_Eh + B + I_abs) and the Def_E + B + I method were 1.21 ± 1.22 Gy α/ß = 3, 1.93 ± 1.38 Gyα/ß = 3, 0.72 ± 1.12 Gyα/ß = 3, and 1.19 ± 1.46 Gyα/ß = 3, respectively. Differences in dose-volume histogram parameter values among Def_E + B + I and other FPA methods were not statistically significant (P > .05). CONCLUSIONS: Compared with the FPA-based method, deformable registration-based dose composites demonstrated lower OAR D2cc and D0.1cc values; however, the differences were not statistically significant. The current ABS-recommended FPA-based sheet can serve as an acceptable plan evaluation tool for clinical purposes.

Comparison of multiparametric MRI-based and transrectal ultrasound-based preplans with intraoperative ultrasound-based planning for low dose rate interstitial prostate seed implantation.

PURPOSE: Transrectal ultrasound images are routinely acquired for low dose rate (LDR) prostate brachytherapy dosimetric preplanning (pTRUS), although diagnostic multiparametric magnetic resonance imaging (mpMRI) may serve this purpose as well. We compared the predictive abilities of TRUS vs MRI relative to intraoperative TRUS (iTRUS) to assess the role of mpMRI in brachytherapy preplanning. MATERIALS AND METHODS: Retrospective analysis was performed on 32 patients who underwent iTRUS-guided prostate LDR brachytherapy as either mono- or combination therapy. 56.3% had pTRUS-only volume studies and 43.7% had both 3T-mpMRI and pTRUS preplanning. MRI was used for preplanning and its image fusion with iTRUS was also used for intraoperative guidance of seed placement. Differences in gland volume, seed number, and activity and procedure time were examined, as well as the identification of lesions suspicious for tumor foci. Pearson correlation coefficient and Fisher's Z test were used to estimate associations between continuous measures. RESULTS: There was good correlation of planning volumes between iTRUS and either pTRUS or MRI (r = 0.89, r = 0.77), not impacted by the addition of hormonal therapy (P = 0.65, P = 0.33). Both consistently predicted intraoperative seed number (r = 0.87, r = 0.86). MRI/TRUS fusion did not significantly increase surgical or anesthesia time (P = 0.10, P = 0.46). mpMRI revealed suspicious focal lesions in 11 of 14 cases not visible on pTRUS, that when correlated with histopathology, were incorporated into the plan. CONCLUSIONS: Relative to pTRUS, MRI yielded reliable preplanning measures, supporting the role of MRI-only LDR treatment planning. mpMRI carries numerous diagnostic, staging and preplanning advantages that facilitate better patient selection and delivery of novel dose escalation and targeted therapy, with no additional surgical or anesthesia time. Prospective studies assessing its impact on treatment planning and delivery can serve to establish mpMRI as the standard of care in LDR prostate brachytherapy planning.

Advances in Radiotherapy for Prostate Cancer Treatment.

Major categories of radiotherapy (RT) for prostate cancer (CaP) treatment are: (1) external beam RT (EBRT), and (2) brachytherapy (BT). EBRT are performed using different techniques like three-dimensional conformal RT (3D-CRT), intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT), stereotactic radiosurgery (SRS) and intensity modulated proton therapy (IMPT), etc., using a variety of radiation delivery machines, such as a linear accelerator (Linac), Cyberknife robotic system, Gamma knife, Tomotherapy and proton beam machine. The primary advantage of proton beam therapy is sparing of normal tissues and organ at risks (OARs) with comparable coverage of the tumor volume. MR-Linac is the latest addition in the image-guided RT. Robot-assisted brachytherapy is one of the latest technological innovations in the field. With the advancement of technology, radiation therapy for prostate cancer can be improved using high quality multimodal imaging, robot-assistance for brachytherapy as well as EBRT. This chapter presents the advances in radiation therapy for the treatment of prostate cancer.

3T multiparametric MRI-guided high-dose-rate combined intracavitary and interstitial adaptive brachytherapy for the treatment of cervical cancer with a novel split-ring applicator.

PURPOSE: To evaluate the role of 3T-MRI-guided adaptive high-dose-rate (HDR) combined intracavitary and interstitial brachytherapy for cervical cancer using a novel intracavitary split-ring (ICSR) applicator adapter. METHODS AND MATERIALS: We retrospectively reviewed all HDR brachytherapy cases from 2013 to 2015 using an ICSR applicator. Initial optimization was performed using 3T multiparametric MRI (mpMRI) series with an applicator in place. The mpMRI series were discretionarily acquired before subsequent fractions for possible target adaptation. When necessary, interstitial needles (ISNs) were inserted through a novel ICSR adapter or freehand. Dosimetric parameters, clinical outcomes, and toxicities were compared between groups. RESULTS: Seventeen patients were included, with a mean followup of 32 months. An mpMRI series preceded each initial fraction and 52.9% of patients underwent ≥1 additional pretreatment mpMRI. Among these subsequent fractions, the high-risk clinical target volume was reduced in 80% vs. 41% without pretreatment mpMRI. Five patients had ISN placement (seven insertions) to improve extracervical target coverage. Mean D90 (Gy) per fraction to the high-risk clinical target volume and intermediate-risk clinical target volume with and without an ISN were 7.51 ± 1.07 vs. 6.14 ± 0.52 (p = 0.028) and 6.35 ± 0.75 vs. 5.21 ± 0.49 (p = 0.007), respectively. Mean fractional D2cc (Gy) for organs at risk was comparable. No Grades 3-4 toxicity was reported. Disease-free survival and local control for the ICSR-ISN and ICSR-alone groups were 29.8 months/80.0% and 31.2 months/83.3%, respectively. CONCLUSIONS: The mpMRI acquisition with ICSR applicator in place immediately before HDR brachytherapy for cervical cancer guided successful adaptive treatment optimization and delivery. Our initial experience with a novel interstitial adapter for the split-ring applicator demonstrated excellent target coverage without compromising organs at risk, resulting in good local control and disease-free survival.

Influence of radiation treatment technique on outcome and toxicity in anal cancer.

OBJECTIVE: Intensity-modulated radiation therapy (IMRT) has largely supplanted three-dimensional conformal radiation (3D-CRT) for definitive anal cancer treatment due to decreased toxicity and potentially improved outcomes. Convincing data demonstrating its advantages, however, remain limited. We compared outcomes and toxicity with concurrent chemotherapy and IMRT vs 3D-CRT for anal cancer. METHODS: We performed a single-institution retrospective review of patients treated with IMRT or 3D-CRT as part of definitive mitomycin-C/5-fluorouricil-based chemoradiation for anal cancer from January 2003 to December 2012. RESULTS: One hundred sixty-five patients were included, with 61 and 104 receiving IMRT and 3D-CRT, respectively. Overall, 92.7% had squamous cell carcinoma. The mean initial pelvic dose was 48.3 and 44 Gy for IMRT and 3D-CRT, respectively. Complete response, partial response, and disease progression rates were similar (IMRT 83.6, 8.2, 8.2%; 3D-CRT 85.6, 6.7, 7.7%; p = 0.608, p = 0.728, p = 0.729). There was no significant difference in overall survival (p = 0.971), event-free survival (p = 0.900), or local or distant recurrence rates (p = 0.118, p = 0.373). IMRT caused significantly less acute grade 1-2 incontinence (p = 0.035), grade 3-4 pain (p = 0.033), and fatigue (p = 0.030). IMRT patients had significantly fewer chronic post-treatment toxicities (p = 0.008), outperforming 3D-CRT in six of eight toxicities reviewed. Though total treatment length was comparable (43.6 and 44.5 days), IMRT recipients had fewer (27.9 vs 41.3% of patients, p = 0.89), shorter treatment breaks (mean 2.9 vs 4.1 days, p = 0.229). CONCLUSION: This report represents the largest series directly comparing concurrent chemotherapy with IMRT vs 3D-CRT for definitive treatment of anal cancer. IMRT significantly reduced acute and post-treatment toxicities and allowed for safe and effective pelvic dose escalation.

The evolving role of radiation therapy in pediatric Hodgkin's disease.

Identifying the optimal treatment of pediatric Hodgkin's disease has been at the forefront of clinical investigation in recent years. Results of a number of large clinical trials have driven paradigm shifts in how physicians approach this often curable disease. In an effort to balance the goals of maximizing survival while minimizing acute toxicities and late complications, the recommended indications, targets, doses and schedules of chemotherapy and radiation have and continue to evolve. Recent attempts to decrease the total volume of tissue receiving radiation without requiring a significant escalation in cytotoxic chemotherapy have shown promise in low, intermediate and high risk patients. Utilizing risk-adapted, response-based treatment, researchers hope to uncover a subpopulation that may not require previously considered standard treatment modalities.

Current topics in the multimodality treatment of locally advanced rectal cancer.

The multimodality approach to the treatment of locally advanced rectal cancer has evolved to include neoadjuvant radiotherapy with or without concurrent chemotherapy, total mesorectal excision and adjuvant fluoropyrimidine-based chemotherapy. Though this broad strategy has yielded improvements in local control compared with historical data, overall survival remains largely unchanged. Current investigations focus on improving patient selection through new imaging modalities, improving surgical techniques, incorporating more aggressive systemic treatment regimens and the selective use of radiation. Here, we review emerging data regarding newer staging techniques, neoadjuvant chemotherapy, optimal timing of surgery, selective use of radiation and nonoperative approaches to the management of locally advanced rectal cancers.

Patterns of cancer recurrence in localized resected hepatocellular carcinoma.

BACKGROUND: Tumor resection in non-metastatic hepatocellular carcinoma (HCC) patients with adequate liver reserve offers a potential cure, but has a high 5-year recurrence rate. We analyzed the patterns of cancer relapse after partial hepatectomy to guide post-operative management. METHODS: A total of 144 HCC patients (1996-2011) after partial hepatectomy were reviewed. Statistical correlations were determined using univariate and partition analyses. RESULTS: A median follow-up of 20 months showed recurrence in 71 (49%) patients, and the median time to recurrence was 11.9 months. Vascular invasion (P<0.01) and number of lesions (P<0.01) predicted for recurrence. Histologic grade was not correlated with recurrence. Twenty-two (31%) patients developed both surgical margin (SM) and concurrent intrahepatic recurrences, and 28 (40%) had non-SM intrahepatic recurrences with no other signs of recurrence. On partition analysis, the risk of marginal recurrence in patients with SM <1 mm and SM ≥1 mm was 35% and 13.5% respectively. Approximately 57% of patients with intrahepatic recurrence had recurrence ≤2.5 cm from SM. CONCLUSIONS: Intrahepatic recurrence after partial hepatectomy is common and is significantly associated with vascular invasion and tumor stage. About 57% of patients with intrahepatic relapse had a recurrence close (≤2.5 cm) to the SM. Additionally, patients with SM <1 mm have a higher recurrence rate and may benefit from adjuvant local therapy.