Evangelia Katsoulakis

A comparative dosimetric analysis of virtual stereotactic body radiotherapy to high-dose-rate monotherapy for intermediate-risk prostate cancer

PURPOSE Stereotactic body radiotherapy (SBRT) is being used with increasing frequency as definitive treatment of early stage prostate cancer. Much of the justification for its adoption was derived from earlier clinical results using high-dose-rate (HDR) brachytherapy. We determine whether HDRs dosimetry can be achieved by virtual SBRT. METHODS AND MATERIALS Patients with intermediate-risk prostate cancer on a prospective trial evaluating the efficacy of HDR monotherapy treated to dose of 9.5Gy×4 fractions were used for this study. A total of 5 patients were used in this analysis. Virtual SBRT plans were developed to reproduce the planning target volume (PTV) HDR dose distributions. Both normal tissue- and PTV-prioritized plans were generated. RESULTS From the normal tissue-prioritized plan, HDR and virtual SBRT achieved similar PTV V100 (93.8% vs. 93.1%, p=0.20) and V150 (40.3% vs. 42.9%, p=0.69) coverage. However, the PTV V200 was not attainable with SBRT (15.2% vs. 0.0%, p<0.001). The rectal Dmax was significantly lower with HDR (94.2% vs. 99.42%, p=0.05). The rectal D2 cc was also lower (60.8% vs. 71.1%, p=0.07). Difference in D1 cc urethral dose was not significantly different (87.7% vs. 75.2%, p=0.33). Comparing the PTV-prioritized plans, the rectal Dmax (94.2% vs. 111.1%, p=0.05) and mean dose (27.1% vs. 33.3%, p=0.03) were significantly higher using SBRT, and the rectal D2 cc was higher using SBRT (60.8% vs. 81.8%, p=0.07). CONCLUSIONS HDR achieves significantly higher intraprostatic doses while achieving a lower maximum rectal dose compared with our virtual SBRT treatment planning. Future studies should compare clinical outcomes and toxicity between these modalities.

Impact of postoperative radiation on survival for high-grade soft tissue sarcoma of the extremities after limb sparing radical resection.

ObjectivesTo use the Surveillance, Epidemiology, and End Results (SEER) Database to analyze the impact of postoperative radiation after limb sparing surgery for high-grade extremity soft tissue sarcomas (STS). MethodsWe identified patients, aged 20 to 79, who were diagnosed between 1988 and 2006 with high-grade STS of the extremities and underwent radical limb sparing surgery with or without postoperative external beam radiation. Kaplan-Meier and Cox regression analyses were performed to evaluate the effect of postoperative external beam radiation therapy on overall survival (OS) and disease-specific survival (DSS). ResultsA total of 983 patients met the selection criteria: 788 (80.2%) received postoperative radiation and 195 (19.8%) underwent surgery alone. For the whole cohort, there were no differences between the groups in OS (P=0.06) or DSS (P=0.20). On subgroup analysis, for tumors ⩽5 cm there remained no significant differences in OS (P=0.8) or DSS (P=0.93). However, for tumors >5 cm the 3-year OS improved with the addition of postoperative radiation from 55.6% to 73.4% (P<0.001). Similarly, the 3-year DSS improved from 68.1% to 80.6% (P=0.005). ConclusionsBecause of the retrospective nature of this study and inherent limitations of the SEER database, a large prospective study is needed to further elucidate the relationship between postoperative radiation and survival. However, these data do support the use of adjuvant radiation for patients with high-grade extremity STS measuring >5 cm.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.

OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumors histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.

Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques

Importance Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials. Objective To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques. Design, Setting, and Participants This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017. Main Outcomes and Measures Patterns of treatment failure and overall survival following locoregional failure or distant metastasis. Results Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P < .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P < .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with oropharyngeal carcinoma negative for human papillomavirus or p16 (median survival, 36.5 vs 13.6 months; P = .007) but not after distant metastasis. Salvage surgery was associated with improved overall survival following locoregional failure (hazard ratio, 0.51; 95% CI, 0.34-0.77; P = .001); oligometastatic disease (1 vs ≥2 lesions: hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001) was associated with improved overall survival following distant metastasis. Conclusions and Relevance Overall survival after recurrence of HNSCC is influenced by the HNSCC subsite and human papillomavirus or p16 status, as well surgical and systemic interventions. An oligometastatic phenotype characterizes patients with solitary metastasis after chemoradiotherapy. These findings have important implications for clinical trial designs for HNSCC in the recurrent and oligometastatic setting.

Delivering a third course of radiation to spine metastases using image-guided, intensity-modulated radiation therapy

OBJECT The objective of this study was to investigate the feasibility and safety of delivering a third course of radiation to patients with multiply recurrent metastatic disease to the spine. METHODS Between 2009 and 2011, 10 patients received a third course of radiation to spinal metastases at Memorial Sloan-Kettering Cancer Center using image-guided intensity-modulated radiation therapy (IMRT). Patient and tumor characteristics, dosimetry details, and outcomes were obtained using retrospective chart review. Spinal imaging was performed prior to treatment and at regular follow-up intervals. The cumulative biologically effective dose (BED) to the spinal cord and cauda equina was calculated and was normalized to 2 Gy equivalents (Gy(2/2)). Toxicity and local control were assessed. RESULTS The median time between the first and second courses of radiation was 18.5 months and the median time between the second and third courses was 11.5 months. The median follow-up from the third course of radiation was 12 months and the median overall survival was 13 months. Pain or neurological symptoms were improved in 80% of patients. The median spinal cord maximum dose normalized BED (nBED) for the whole cohort was 70.73 Gy(2/2) (range 51.9-101.7 Gy(2/2)). The median dose to 5% of the spinal cord D(05) nBED for the entire cohort was 59.4 Gy(2/2). Acute toxicity was most commonly fatigue and dermatitis, with 1 patient experiencing Grade 3 fatigue and 1 patient Grade 3 dermatitis. Late toxicity was limited to 2 cases of Grade 1 dysphagia. There was 1 case of Grade 1 neuropathy and 1 case of Grade 2 neuropathy. The crude rate of local control was 80% with 1 in-field failure and 1 marginal failure. CONCLUSIONS In this cohort of patients, a third course of IMRT to the spine was well tolerated with no significant late toxicities. Used as salvage therapy for select patients, a third course of radiation is a safe and effective treatment strategy.

Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy’s local control superior?

Abstract Background. The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980’s reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution’s results of photon radiotherapy for unresectable salivary gland tumors. Patients and methods. From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. Results. With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient’s experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. Conclusions. Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery.

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

Temporary organ displacement coupled with image-guided, intensity-modulated radiotherapy for paraspinal tumors

BackgroundTo investigate the feasibility and dosimetric improvements of a novel technique to temporarily displace critical structures in the pelvis and abdomen from tumor during high-dose radiotherapy.MethodsBetween 2010 and 2012, 11 patients received high-dose image-guided intensity-modulated radiotherapy with temporary organ displacement (TOD) at our institution. In all cases, imaging revealed tumor abutting critical structures. An all-purpose drainage catheter was introduced between the gross tumor volume (GTV) and critical organs at risk (OAR) and infused with normal saline (NS) containing 5-10% iohexol. Radiation planning was performed with the displaced OARs and positional reproducibility was confirmed with cone-beam CT (CBCT). Patients were treated within 36 hours of catheter placement. Radiation plans were re-optimized using pre-TOD OARs to the same prescription and dosimetrically compared with post-TOD plans. A two-tailed permutation test was performed on each dosimetric measure.ResultsThe bowel/rectum was displaced in six patients and kidney in four patients. One patient was excluded due to poor visualization of the OAR; thus 10 patients were analyzed. A mean of 229 ml (range, 80–1000) of NS 5-10% iohexol infusion resulted in OAR mean displacement of 17.5 mm (range, 7–32). The median dose prescribed was 2400 cGy in one fraction (range, 2100–3000 in 3 fractions). The mean GTV Dmin and PTV Dmin pre- and post-bowel TOD IG-IMRT dosimetry significantly increased from 1473 cGy to 2086 cGy (p=0.015) and 714 cGy to 1214 cGy (p=0.021), respectively. TOD increased mean PTV D95 by 27.14% of prescription (p=0.014) while the PTV D05 decreased by 9.2% (p=0.011). TOD of the bowel resulted in a 39% decrease in mean bowel Dmax (p=0.008) confirmed by CBCT. TOD of the kidney significantly decreased mean kidney dose and Dmax by 25% (0.022).ConclusionsTOD was well tolerated, reproducible, and facilitated dose escalation to previously radioresistant tumors abutting critical structures while minimizing dose to OARs.

Hypopharyngeal squamous cell carcinoma: Three‐dimensional or Intensity‐modulated radiotherapy? A single institution's experience

Compare outcomes of hypopharyngeal carcinoma that received conventional radiotherapy versus intensity‐modulated radiotherapy (IMRT).

Image-guided radiation therapy for liver tumors: gastrointestinal histology matters.

Objectives:To describe the safety and efficacy of single-fraction and hypofractionated image-guided radiotherapy techniques for the treatment of large liver tumors. Methods:Forty-six patients, with 50 tumors (10 primary liver tumors, 40 liver metastases) from March 2004 to March 2011 were reviewed. The maximal tumor diameter ranged from 1.2 to 11.3 cm (median, 4.2 cm). Eighty-seven percent of patients received prior systemic chemotherapy. Fifty-nine percent had prior invasive local therapy including surgery, ablation, or embolization. Twenty-five lesions were treated with hypofractionated therapy (24 to 30 Gy in 3 to 5 fractions), whereas 19 received a single fraction (18 or 24 Gy). Local control (LC) was calculated using competing risk analysis. Overall survival was calculated by the Kaplan-Meier method. Results:Median follow-up for all patients was 29.8 months (range, 3 to 46 mo). The median survival was 15.4 months. The 1- and 2-year LC rates were 78% and 75%, respectively. Dose and tumor size had no significant effect on tumor progression. The local progression at 1 and 2 years was 29% and 32% for gastrointestinal (GI) histologies versus 0% for non-GI histologies (P=0.02). Tumor volumes larger than 112 cm3 correlated with decreased survival (P=0.05). Three patients developed late grade 3 GI stricture or ulceration. Conclusions:Image-guided radiotherapy for liver tumors achieves good rates of LC with minimal toxicity at 1 and 2 years even in patients with large or recurrent disease that has been heavily pretreated. GI histology demonstrated decreased LC rates. Further management strategies should be considered in these patients.