Long-Term Clinical and Cosmetic Outcomes of Once-Daily Accelerated Partial Breast Irradiation in Early Breast Cancer.

Purpose: Accelerated partial breast irradiation (APBI) is one of the standard treatment options in early-stage node negative breast cancer in selected patients. However, the optimal dose fractionation schedule still represents a challenge. We present the 12-year follow up results of clinical and cosmetic outcomes of once daily APBI with external beam radiation therapy which provides an APBI radiation dose equivalent to the whole breast radiation with a boost. Methods and Materials: From July 2008 to August 2010, we enrolled 34 patients with T1, T2 (< 3cm) N0 to receive once daily APBI with three dimensional conformal radiation therapy (3D-CRT) to a total dose of 49.95 Gy over 15 single daily fractions over 3 weeks at 3.33 Gy per fraction. Ipsilateral breast tumor recurrence (IBTR), acute toxicity, late toxicity and cosmesis was analyzed. The median follow-up for all patients is 144 months (12 years). Results: The median age of the patients was 61 years (range 46-83). Nine patients had ductal carcinoma in situ (DCIS) and 25 patients had invasive cancer. The median size of the tumor with DCIS pathology was 0.5 cm, while median size of the tumor with invasive cancer pathology was 1.0 cm. All of the patients had negative margins and negative nodes. Two IBTR was observed (5.8%). One patient had DCIS at recurrence and other had invasive recurrence. Two patients died due to non-cancer cause. The 12-year actuarial ipsilateral breast recurrence free survival was 93.5% and the 12-year actuarial overall survival was 93.2%. Late Grade 2 toxicity was observed in 6 patients and late grade 3 toxicity was seen in 1 patient. 91% of the patients had excellent to good cosmesis. Conclusions: This novel APBI dosing schema is based on an equivalent dose compared to whole breast radiation plus a tumor bed boost. This once daily APBI scheme is well-tolerated and demonstrates good to excellent cosmetic outcome and low rates of late complications on long term follow-up.

Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Interstitial Brachytherapy Is Safe: First Results From the Tri-fraction Radiation Therapy Used to Minimize Patient Hospital Trips (TRIUMPH-T) Trial.

PURPOSE: Shorter courses of breast radiotherapy are offered as an alternative to 4 weeks of whole-breast irradiation after lumpectomy, including brachytherapy. A prospective phase 2multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation delivered by brachytherapy was conducted. METHODS AND MATERIALS: The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥45 years with unicentric invasive or in situ tumors ≤3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. RESULTS: Two hundred patients were prospectively enrolled; however, a total of 185 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 94% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). CONCLUSIONS: Ultra-short breast brachytherapy is feasible and has excellent toxicity and could be an alternative to standard 5-day, 10 fraction accelerated partial breast irradiation in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long-term outcomes.

Integration of Radiation and Reconstruction After Mastectomy.

Postmastectomy radiation therapy (PMRT) is a mainstay of local therapy for many breast cancer patients. Patients undergoing mastectomy typically are offered options for breast reconstruction. For patients who are candidates for PMRT, there are ongoing challenges with combining optimal radiation technique to prioritize oncologic outcomes, against the goals of minimizing toxicity and achieving the best reconstruction outcomes. The process by which these decisions are made continues to evolve as surgical and radiation techniques have improved and expanded, and as more patients with different risk profiles for local recurrence are receiving PMRT. We review the considerations regarding the different types of reconstruction and timing with radiation treatment. We also review the technical radiation consideration such as dose-fractionation, use of bolus and scar boost, exploring the controversies associated with the nuanced decisions regarding radiation and reconstructive surgery which are influenced by variables that are under continued investigation.

Does the Use of BioZorb® Result in Smaller Breast Seroma Volume?

AIM: To evaluate the impact of BioZorb®, a 3D-bioabsorbable marker, on the tumor-bed boost volume and dosimetric parameters in adaptive boost planning for breast cancer. PATIENTS AND METHODS: Records were reviewed for 51 breast-cancer patients who underwent breast-conserving surgery and adjuvant whole-breast irradiation between January 2017 and October 2018. Changes in lumpectomy boost volume (LBV), doses to organs at risk, toxicity and cosmesis were compared between patients with and without BioZorb® Chi-square test and paired and independent t-tests were used for comparisons of variables. RESULTS: Median follow-up was 35.5 months. Mean LBV on initial CT (LBV1; 32.2 vs. 33.8 cc, p=0.74) and on boost computed tomography (CT) (LBV2; 25.3 vs. 24.8 cc, p=0.87) were similar with and without BioZorb® The mean decrease from LBV1 to LBV2 was 9.0 cc and 6.8 cc with and without BioZorb®, respectively (p=0.42). LBV1 was significantly positively correlated with a 20% reduction in LBV (p=0.02). Mean heart and lung doses on adaptive boost planning CT were slightly lower compared to initial planning CT in both groups. Acute breast pain was reported in 18/51 patients, 9 of whom had BioZorb® (p=0.24). Grade-2 pain was reported in 5/51 patients, 3 of whom had BioZorb® (p=0.11). Excellent or good cosmesis was reported in 36/41 patients. Fair cosmesis was reported in 5/41 patients, of whom 2 had BioZorb® (p=0.64). CONCLUSION: BioZorb® placement does not impact the tumor-bed boost volume nor the variation of seroma volume within the period of treatment. More data and longer follow-up are needed to identify a measurable clinical impact of BioZorb® placement.

Adaptive Lumpectomy Boost Planning Can Reduce Normal Tissue Exposure in Patients Receiving Hypofractionated Whole Breast Irradiation.

BACKGROUND/AIM: To evaluate the change in lumpectomy cavity (LPC) volume during hypofractionated radiation (Hypo-RT) and assess the dosimetric benefits of adaptive boost planning on normal tissue exposure in breast cancer patients. PATIENTS AND METHODS: Two separate computed tomography (CT) simulation scans were obtained. The first (CT1) was used to plan whole breast irradiation, and the second (CT2) was used to plan LPC boost. LPC boost treatment planning was performed on both CT1 and CT2. RESULTS: Mean LPC volume was significantly smaller on CT2 compared to CT1. LPC boost plan comparison showed significant reductions from CT1 to CT2 in mean heart dose and mean lung dose. Mean volume of tissue receiving 95% of the prescribed boost dose (V95) was lower on CT2 (p=0.001), as was V80 (p<0.001) and V50 (p<0.001). CONCLUSION: LPC volume can change significantly during Hypo-RT. Adaptive LPC boost planning can be considered to reduce normal tissue exposure.

Impact of the Coronavirus Disease of 2019 Pandemic on Radiation Oncology Clinical Decision Making in a High-Prevalence Environment.

PURPOSE: This study aimed to define how the coronavirus disease of 2019 (COVID-19) pandemic affected the role, timing, and delivery of radiation therapy (RT) in a high-prevalence region at the height of the initial U.S. outbreak. METHODS AND MATERIALS: We performed a retrospective review of all patients seen at 3 radiation oncology departments within the Rutgers Robert Wood Johnson Barnabas Health system in New Jersey during the initial COVID-19 surge. The primary endpoints were to define and quantify COVID-related, radiation-specific care changes, and identify predictive factors of experiencing COVID-related care changes. RESULTS: A total of 545 patients with cancer were seen during the study period, 99 of whom (18.1%) experienced ≥1 COVID-related care change. RT delays were the most common, accounting for 51.5% of all care changes. Physician-directed delays accounted for 41.2% of RT delays, and patient fears, COVID testing, and access barriers were responsible for 27.5%, 17.6%, and 13.7%, respectively. Patient age (P = .040), intent of treatment (P = .047), and cancer type (P < .001) were significantly associated with experiencing a COVID-related care change, as we found that older, curative intent and patients with rectal cancer were more likely to experience care changes. On multivariate analysis, patient age remained significant when controlling for treatment intent and cancer type. CONCLUSIONS: Our study provides a perspective on how care was adapted to protect patients with cancer during a pandemic while maximizing disease control. The positive correlation between age and likelihood of care changes may reflect extra precaution taken with older patients given their vulnerability to severe COVID illness. The lower observed likelihood of COVID-related care changes among patients undergoing palliative RT may reflect either the more urgent needs addressed by palliative RT or simply be logistical, because palliative radiation is often delivered in short courses with less exposure risk. Assessing adaptations others have implemented and monitoring how they affect patient outcomes will be crucial.

Hypofractionated Postmastectomy Radiation Therapy.

PURPOSE: To provide an overview of the major randomized trials that support the use of hypofractionated post-mastectomy radiation therapy for locally advanced breast cancer patients. METHODS AND MATERIALS: PubMed was systematically reviewed for publications reporting use of of hypofractionated radiation therapy in patients requiring post-mastectomy radiation. RESULTS: Standard fractionation, which is typically delivered over 5 to 7 weeks, is considered the standard of care in setting of post-mastectomy radiation therapy (PMRT). Modern data has helped to establish hypofractionated whole breast irradiation, which consists of a 3- to 4-week regimen, as a new standard of care for early-stage breast cancer. Hypofractionated whole breast irradiation has also laid the groundwork for the exploration of a hypofractionated approach in the setting of hypofractionated post-mastectomy radiation therapy. CONCLUSIONS: While standard fractionation remains the most commonly utilized regimen for PMRT, recently published trials support the safety and efficacy of a hypofractionated approach. Ongoing trials are further investigating the use of hypofractionated PMRT.

Multi-institutional Investigation: Circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam radiation in mycosis fungoides.

BACKGROUND AND PURPOSE: A lower proportion of CD8+ tumor infiltrating lymphocytes in mycosis fungoides (MF) patients is associated with worse survival. However, it is not known whether circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam therapy (TSEBT). METHODS AND MATERIALS: We identified 126 MF patients treated with TSEBT from 2001 to 20014 at two high-volume academic centers. Circulating CD4:CD8 ratio was obtained within 1 week before TSEBT. TSEBT was delivered with 6-9mEV electrons with low (12 Gy) or conventional (≥12 Gy) doses. Treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) while mSWAT decrease of <75% was considered partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in the derivation cohort and was applied to an external validation cohort. RESULTS: 71.4% and 28.6% of patients achieved CR and PR after TSEBT. Higher CD4:CD8 ratio predicted poorer response: median CD4:CD8 in patients with PR vs. CR was 4.84 vs. 1.97 (p = 0.002). A threshold CD4:CD8 of 4.42 optimally discriminated in the discovery cohort patients with PR vs. XR (sensitivity 90%, specificity 59%, area under curve (AUC) = 0.71; p = 0.002). Within an independent test cohort (n = 32), 73.9% of patients with CD4:CD8 <4.42 achieved CR vs. 33.3% of those with CD4:CD8 ≥4.42 (p = 0.033). Among all patients with CD4:CD8 <4.42 (n = 73), 74% achieved CR with low-dose TSEBT vs. 93% with conventional dose TSEBT (p = 0.02). On multivariable logistic regression, CD4:CD8 remained a significant independent predictor of TSEBT response in all patients (OR = 0.107, 95% CI 0.395-0.290, p < 0.001). CONCLUSION: Peripheral blood CD4:CD8 ratio was a significant independent predictor of TSEBT response of MF patients as validated in an independent cohort at separate academic center. The potential for CD4:CD8 ratio as a biomarker to inform radiation treatment dosing warrants further investigation.

Using benchmarked lung radiation dose constraints to predict pneumonitis risk: Developing a nomogram for patients with mediastinal lymphoma.

PURPOSE: We identified lung dosimetric constraints to assist in predicting the radiation pneumonitis (RP) risk in patients with mediastinal lymphoma and then identified the clinical prognostic factors that were associated with the achievement of key dosimetric constraints. METHODS AND MATERIALS: In 190 patients who received mediastinal intensity modulated radiation therapy, we used univariate χ2 and multivariate logistic models to identify the predictors of RP and achievement of lung dose-volume histogram (DVH) constraints and build a predictive nomogram for RP. RESULTS: An increased risk of RP was strongly associated with mean lung dose (MLD) > 13.5 Gy (odds ratio [OR]: 8.13; 95% confidence interval [CI], 3.01-21.93; P < .001) and the percent of lung volume receiving ≥5 Gy (V5) > 55% (OR: 7.01; 95% CI, 2.94-16.72; P < .001). Therefore, patients had low RP risk (8%) if both MLD ≤13.5 and V5 ≤55 constraints were achieved, moderate risk (24%) if only MLD was achieved, and the highest risk (48%) if MLD was not achieved. Deep-inspiration breath-hold (DIBH) technique during treatment strongly prognosticated achieving MLD and V5 DVH constraints (OR,3.88; 95% CI, 1.84-8.19; P < .001). Specifically, 86% of patients who were treated with DIBH versus 63% without DIBH achieved DVH constraints (P < .001). This translated into a "number needed to treat" with DIBH of 4 patients to enable 1 additional patient to achieve both constraints. In comparison, the clinical characteristics were marginal prognosticators: DVH constraints were more likely achieved in nonbulky disease (OR: 3.01; 95% CI, 0.89-4.53; P = .09) and patients who had not previously received salvage chemotherapy (OR, 2.44; 95% CI, 0.98-6.11; P = .06). Nomogram-predicted risks of RP ranged from 4% to 60% on the basis of MLD and V5, total radiation dose, and use of salvage chemotherapy. CONCLUSIONS: Achieving mean lung and V5 DVH constraints is critical to reduce RP risk in patients with lymphoma who receive mediastinal intensity modulated radiation therapy. The use of the DIBH technique is a promising risk-modifying treatment approach in patients with mediastinal lymphoma and especially in patients with a history of nonmodifiable risk factors for RP such as bulky disease and salvage chemotherapy.

Effectiveness of low-dose radiation for primary cutaneous anaplastic large cell lymphoma.

PURPOSE: Primary cutaneous anaplastic large cell lymphoma (pcALCL) is conventionally treated with radiation therapy (RT) doses ≥30 GGy, but effectiveness of lower doses is unclear. We compared responses after a range of RT doses for pcALCL. METHODS AND MATERIALS: From 1999 through 2015, 45 lesions in 21 patients met clinicopathologic pcALCL diagnostic criteria and were treated with RT (<20 Gy, 20-29 Gy, or ≥30 Gy dose). Complete clinical (CR) and partial responses (PR) were compared by dose using Fisher exact test. Progression-free and overall survivals were calculated using the Kaplan-Meier method. RESULTS: Forty-two percent of lesions were treated with <20 Gy, 22% with 20 to 29 Gy, and 35% with ≥30 Gy. Within 12 weeks, 100% responded, with 67% CR and 33% PR; by last follow-up, 87% achieved CR and 13% PR (no difference by RT dose; P = .84). Three-year freedom from local relapse was 100%, 86%, and 100% with <20 Gy, 20 to 29 Gy, and ≥30 Gy, respectively (P = .28). Many patients ultimately demonstrated other cutaneous or systemic relapse, with 55% 3-year and 29% 10-year progression-free survival. Overall survival at 10 years was 59%, with 2 deaths from complications of disease. CONCLUSIONS: Low-dose RT offered excellent local control in the setting of the indolent, chronic course of pcALCL in this patient cohort.

Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment.

PURPOSE/OBJECTIVE(S): Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT. METHODS AND MATERIALS: We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed. RESULTS: Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic leukemia (22%), chronic lymphocytic leukemia (3%), chronic myelocytic leukemia (14%), lymphoma (11%), and myeloma (3%). CSI was used for consolidation (30 patients, 81%) and gross disease treatment (7 patients, 19%). Median radiation dose (interquartile range) was 24 Gy (23.4-24) for photons and 21.8 Gy (21.3-23.6) for protons (P = .03). Proton CSI was associated with lower rates of Radiation Therapy Oncology Group grade 1-3 mucositis during CSI (7% vs 44%, P = .03): 1 grade 3 with protons versus 5 grade 1, 3 grade 2, and 2 grade 3 with photons. During CSI, other toxicities (infection, gastrointestinal symptoms) did not differ. Allogeneic stem cell transplant (SCT) was used in 95% of patients, with 53% of patients in remission before SCT. Myeloablative conditioning was used for 76%. During SCT admission and 100 days post-SCT, toxicities did not differ by CSI technique. Successful engraftment occurred in 95% of patients (P = .67). Progression or death occurred for 47% of patients, with only 1 CNS relapse. CONCLUSION: In our cohort, CSI offered excellent local control for CNS-involved hematologic malignancies in the pre-SCT setting. Acute mucositis occurred less frequently with proton CSI with comparable peritransplant/long-term toxicity profile, suggesting the need to further explore the benefit/toxicity profile of this technique.

Chemotherapy Response Assessment by FDG-PET-CT in Early-stage Classical Hodgkin Lymphoma: Moving Beyond the Five-Point Deauville Score.

PURPOSE: In early-stage classical Hodgkin lymphoma, fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans are performed routinely after chemotherapy, and the 5-point Deauville score is used to report the disease response. We hypothesized that other PET-CT parameters, considered in combination with Deauville score, would improve risk stratification. METHODS AND MATERIALS: Patients treated for stage I to II Hodgkin lymphoma from 2003 to 2013, who were aged ≥18 years and had analyzable PET-CT scans performed before and after chemotherapy, were eligible. The soft tissue volume (STV), maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were recorded from the PET-CT scans before and after chemotherapy. Reductions were defined as 1 - (final PET-CT value)/(corresponding initial PET-CT value). The primary endpoint was freedom from progression (FFP). RESULTS: For 202 patients treated with chemotherapy with or without radiation therapy, the 5-year FFP was 89% (95% confidence interval 85%-93%). All PET-CT parameters were strongly associated with the Deauville score (P<.001) and FFP (P<.0001) on univariate analysis. The Deauville score was highly predictive of FFP (C-index 0.89) but was less discriminating in the Deauville 1 to 4 subset (C-index 0.67). Therefore, we aimed to identify PET-CT parameters that would improve risk stratification for this subgroup (n=187). STV reduction was predictive of outcome (C-index 0.71) and was dichotomized with an optimal cutoff of 0.65 (65% reduction in STV). A model incorporating the Deauville score and STV reduction predicted FFP more accurately than either measurement alone in the Deauville 1 to 4 subset (C-index 0.83). The improvement in predictive accuracy of this composite measure compared with the Deauville score alone met statistical significance (P=.045). CONCLUSIONS: The relative reduction in tumor size is an independent predictor of outcome. Combined with the Deauville score, it might improve risk stratification and contribute to response-adapted individualization of therapy.

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation.

PURPOSE: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). METHODS AND MATERIALS: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. RESULTS: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. CONCLUSIONS: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.

Outcomes After Chemotherapy Followed by Radiation for Stage IIB Hodgkin Lymphoma With Bulky Disease.

BACKGROUND: Treatment of stage IIB bulky Hodgkin lymphoma (HL) is controversial, with treatment varying by institution. We evaluated patients with IIB bulky disease treated with combined-modality therapy at our institution by describing their long-term outcomes. PATIENTS AND METHODS: We identified 149 consecutive patients with stage IIB bulky HL treated between 1971 and 2012. Clinical, pathologic, and treatment characteristics were extracted from medical records. Actuarial overall survival (OS) and relapse-free survival (RFS) were calculated by the Kaplan-Meier method. Independent factors associated with these outcomes were identified by a multivariate Cox regression model. Outcomes were further compared against comparison groups of both advanced-stage and stage IIB patients treated between 1971 and 2009. RESULTS: The 8-year OS rate for patients with stage IIB bulky disease who received combined-modality ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and radiation was 88.8%; the 8-year RFS rate was 76.8%. On multivariate analysis, age < 40 years (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.14-0.57; P = .001), receipt of ABVD (vs. MOPP [mechlorethamine, vincristine, procarbazine, prednisone]; HR, 0.32; 95% CI, 0.10-0.88; P = .028), and radiation dose ≥ 30.1 Gy (HR, 0.25; 95% CI, 0.11-0.65; P = .006) were associated with improved OS. Cardiac events (n = 11) and secondary malignancies (n = 11) only occurred in patients treated before 1995. A subgroup analysis demonstrated significantly improved survival in IIB bulky versus advanced-stage patients (8-year OS, 73.4% vs. 57.4%; P = .008). Improved outcomes in patients with in IIB bulky disease were especially evident in the modern era (> 1995; P = .004). CONCLUSION: Patients with stage IIB bulky HL had excellent outcomes after combined-modality therapy. Treatment strategies have changed substantially over time, with concomitant improvements in disease outcomes and long-term toxicities.

Challenges in combining antiangiogenic therapy with transarterial chemoembolization for hepatocellular carcinoma.

BACKGROUND: The combination of systemic antiangiogenic therapy and transarterial chemoembolization (TACE) for the treatment of unresectable hepatocellular carcinoma (HCC) is the subject of several ongoing clinical trials. We present a series of patients treated with sorafenib and TACE at our institution, highlighting the technical challenges of combining these two modalities of treatment. METHODS: We retrospectively identified patients with HCC treated with TACE and sorafenib at our institution. RESULTS: Five patients were treated with the combination of TACE and sorafenib given off-protocol based on preliminary reports in the literature. The first four patients started sorafenib 7 days prior to TACE resulting in intratumoral vascular pruning and poor visualization of lesions on angiography. This was managed by either superselective angiography or lobar TACE. The fifth patient stopped sorafenib 7 days prior to TACE with full visualization of multiple hypervascular lesions on angiography prior to embolization. CONCLUSIONS: Our observations suggest that the biologically preferable strategy of continuous antiangiogenic therapy should be weighed against the possibility of suboptimal TACE due to poor visualization of lesions on angiography and safety.