Received Intensity Modulated Radiation Therapy Research Articles

Late toxicity after post-prostatectomy intensity modulated radiation therapy: Evaluating normal-tissue sparing guidelines

PurposeDose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. Methods and materials164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated. ResultsWith a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. ConclusionsMore than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy.

The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively. Multivariate Cox regression analysis identified that targeted treatment [hazard ratio (95% confidence interval), 2.642 (1.001, 6.972); P=0.0497] served as an independent negative prognostic factor in locally advanced NPC. The results of immunostaining revealed that the staining intensity of the radiation-resistant group was increased compared with that of the radiation-sensitive group. These results demonstrate that a high expression of EGFR may be associated with radiation resistance, and targeted treatment may not be effective in patients with locally advanced nasopharyngeal carcinoma with low expression of EGFR.

GSTP1 Ile105Val polymorphism might be associated with the risk of radiation pneumonitis among lung cancer patients in Chinese population: A prospective study.

Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conducted a prospective study to evaluate the associations between functional SNPs and risk of RP.Methods: We recruited a total of 149 lung cancer patients who had received intensity modulated radiation therapy (IMRT). GSTP1 and XRCC1 were genotyped using the SurPlexTM-xTAG method in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Cox proportional hazard regression was performed to identify clinical variables and SNPs associated with risk of RP grade ≥ 2, using univariate and multivariate analysis, respectively.Results: With a median follow-up of 9 months, the incidence of RP of grade ≥ 2 was 38.3%. A predicting role in RP was observed for the GSTP1 SNP (adjusted hazard ratio 3.543; 95% CI 1.770-7.092; adjusted P< 0.001 for the Ile/Val and Val/Val genotypes versus Ile/Ile genotype). Whereas, we found that patients with XRCC1 399Arg/Gln and Gln/Gln genotypes had a lower risk of RP compares with those carrying Arg/Arg genotype (adjusted HR 0.653; 95% CI 0.342-1.245), but with no statistical significance observed (adjusted P = 0.195).Conclusions: Our results suggested a novel association between GSTP1 SNP 105Ile/Val and risk of RP development, which suggests the potential use of this genetic polymorphism as a predictor of RP. In addition, genetic polymorphisms of XRCC1 399Arg/Gln may also be associated with RP.

Patient Reported Comparative Effectiveness of Contemporary Intensity Modulated Radiation Therapy Versus External Beam Radiation Therapy of the Mid 1990s for Localized Prostate Cancer

IntroductionLittle is known about differences in patient reported outcomes between contemporary external beam radiation therapy for localized prostate cancer that delivers higher doses of conformal radiation and older techniques. We examined sexual, urinary and bowel function between men undergoing contemporary intensity modulated radiation therapy vs those undergoing external beam radiation therapy in the mid 1990s. MethodsSubjects were selected from 2 large population based prospective cohort studies. Main outcomes were between-group differences in adjusted mean scores at 6 and 12 months. Secondary analyses examined odds ratios comparing groups reporting a clinically significant decline in function. ResultsThe cohort consisted of 943 men, 467 diagnosed in 2011 to 2012 and 476 diagnosed in 1994 to 1995. Men undergoing contemporary intensity modulated radiation therapy reported better bowel function at 6 months (mean difference 4.3 points, 95% CI 1.6–7.0) but not at 12 months. Patients receiving contemporary intensity modulated radiation therapy reported statistically worse but probably not clinically meaningful different urinary function at 12 months (2.7, 0.5 to 4.8 points), and no difference at 6 months. No differences in sexual function at 6 or 12 months were found. Secondary analyses demonstrated lower odds of reporting clinically meaningful declines in bowel function at 6 and 12 months and sexual function at 12 months for contemporary intensity modulated radiation therapy. However, patients receiving intensity modulated radiation therapy had higher odds of reporting clinically meaningful declines in urinary continence at 12 months. ConclusionsDespite the delivery of higher doses of radiation, men treated with contemporary intensity modulated radiation therapy reported fewer gastrointestinal and possibly fewer sexual side effects than those treated with external beam radiation therapy in the mid 1990s. However, delivery of dose escalated intensity modulated radiation therapy may cause more urinary side effects.

High Risk Oral Cavity Carcinoma Patient Outcomes Following Minimally Invasive Surgery and Adjuvant Radiation

There has been a significant rise in the utilization of less invasive surgical treatment for oropharyngeal and oral cavity squamous cell carcinomas. Transoral laser microsurgery (TLM) has become an increasingly common procedure for primary treatment of oral cavity squamous cell carcinoma (OCSCC) due to improved cosmetic and functional outcomes. To date, little reported data exists addressing the outcomes of patients with OCSCC following TLM, especially those treated with adjuvant radiation therapy. The aim of this study was to retrospectively review the outcomes of patients with OCSCC treated with TLM and adjuvant radiation therapy. A single institutional retrospective chart review of patients diagnosed with OCSCC treated with TLM, with or without neck dissection, and adjuvant radiation therapy was conducted. All patients with a previous or concurrent diagnosis of oropharyngeal squamous cell carcinoma were excluded from our review. Treatment outcomes including local/regional control (LRC), overall survival (OS), and treatment toxicity were evaluated. These results were then compared to historical, published outcome data for treatment of OCSCC. Kaplan-Meier method was used to estimate 1, 3, and 5 year survival and freedom from local regional recurrence, and log-rank test was used to compare the freedom from events rate between groups. Thirty-nine patients meeting our inclusion criteria diagnosed with OCSCC from 1997 to 2015 were identified. Of these, 20 patients had AJCC stage III/IV disease at presentation, and the additional 19 patients had “high risk” features (68% recurrent disease, 32% depth of invasion ≥ 4mm, 21% perineural invasion, 11% positive margins, and 5% lymphovascular space invasion). The majority of patients (82%) received intensity modulated radiation therapy (IMRT), and 36% also received concurrent chemotherapy. Median follow-up for all patients was 26 months (range 2-155 months). The five year LRC rate was 65% overall, 58% for patients with recurrent disease, and 64% for patients with stage III/IV disease. The five year OS rate was 50% for advanced stage patients. The five year rates of LRC of 65% and OS of 41% in the “high risk” early T-classification cohort were consistent with historical rates of LRC(53 -69%) and OS (25 -63%). There was a 7.7% incidence of grade 3 osteoradionecrosis, which predominately occurred in the patients with recurrent disease, including one case of reirradiation. Our institutional outcomes of this retrospective cohort of patients with oral cavity cancer treated with TLM and radiation therapy are consistent with historical data. TLM should be considered a viable option to traditional wide local excision.

Long-Term Survival in Oligometastatic Head and Neck Cancer

Aggressive therapies for patients with a limited burden of metastatic disease are increasingly being administered with definitive intent in the context of clinical trials. However, outcomes in oligometastatic head and neck squamous cell carcinoma (HNSCC) patients have not been well characterized. We reviewed outcomes from 1147 patients who received intensity modulated radiotherapy (IMRT) as part of definitive management for stage I-IVB HNSCC from 2001-2013 at our institution. The primary sites included oropharynx (OPC, n = 735), oral cavity (OCC, n = 182), larynx (LRX, n = 180) and hypopharynx (HPX, n = 50). Among patients who developed distant metastatic recurrence (DM), the burden of disease was assessed by enumeration of the number of clinically or radiographically apparent tumors. Survival estimates following DM were generated using the Kaplan-Meier method and compared using log-rank testing. Cox proportional hazards models were used for univariate (UVA) and multivariate analyses (MVA). A total of 148 (13%) patients developed DM at a median time of 10.7 months (range 0.3-81.2) after IMRT. The cohort included 88 OPC, 21 OCC, 25 LRX and 14 HPX patients. The median follow-up time following DM was 48 months (range 4-131). At the time of metastasis, the median age was 61 (range 28-88), and the median Karnofsky performance status (KPS) was 80 (range 50-100). 5-year survival following DM was significantly longer in patients with a solitary metastatic lesion compared to multiple lesions (Table 1, P = 0.001). No statistically significant differences in survival were seen by pairwise comparisons of patients with 2 vs 3 vs 4 vs 5+ lesions. Of the 19 patients with solitary metastasis, 14 underwent definitive local therapy to the metastatic site with either surgery or radiotherapy. Patients who received definitive local therapy for a solitary metastasis survived longer than those who did not (5-year survival 55.7% vs 0%, P = 0.001), though the patients who did not receive local therapy were of poorer KPS. On UVA and MVA, longer survival after DM was associated with KPS>70, receipt of palliative cetuximab, non-OCC primary, longer time to metastasis and solitary metastatic tumor (MVA hazard ratio 0.31, 95% CI 0.16-0.59, P = 0.001). An oligometastatic phenotype characterizes HNSCC patients with solitary metastasis, demonstrated by a significant proportion of patients surviving 5+ years following the diagnosis of metastatic disease. These findings have important implications regarding clinical trial design for HNSCC in the recurrent and oligometastatic setting.Abstract 296; Table 1Five-year survival following distant metastasis (DM) according to number of metastatic lesions at time of DM# of metastatic lesionsN5-year survival following DM (±Std. error)11939.1% (±12.6%)2317.9% (±5.3%)3205.7% (±5.5%)4110%5+670% Open table in a new tab

High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in Southern China and Southeast Asia compared with Western countries. The standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to satisfactory treatment, it can cause local recurrence and distant metastases in some patients after treatment by radiation. We retrospectively reviewed 108 NPC patients (7th AJCC Ⅲ-Ⅳa) who have received intensity modulated radiation therapy (IMRT) between August 2008 and January 2012 at Xiangya Hospital of Central South University. Ninety-eight patients with >60% reduction of tumor size after radiation treatment were regarded as radiation sensitive, Ten patients with <40% reduction of tumor size after radiation treatment were regarded as radiation resistant. Using immunohistochemistry, we found that the high expression rate of Ki-67 in radiation resistant and radiation sensitive patients was 80.0% and 42.6%, respectively, and the difference was statistically significant (p = 0.025). The 5-year progress free survival rates in patients with low and high expression of Ki-67 was 70.7% and 48.0%, respectively, and the difference was statistically significant (p = 0.0008). Multivariate Cox regression analysis identified that high expression of Ki-67 was an independent negative prognostic factor in nasopharyngeal carcinoma patients [Hazard ratio (95% CI), 2.098(1.101, 3.996); p = 0.024]. These results demonstrate that high expression of Ki-67 contributes to radiation resistance and acts a poor prognosis indicator in patients with locally advanced nasopharyngeal carcinoma.

Long-term survival in oligometastatic head and neck cancer patients.

6029 Background: Aggressive therapies for patients with oligometastatic disease are increasingly being administered with definitive intent in the context of clinical trials. However, outcomes in oligometastatic head and neck squamous cell carcinoma (HNSCC) patients have not been well characterized. Methods: We reviewed outcomes from 1147 patients who received intensity modulated radiotherapy (IMRT) as part of definitive management for stage I-IVB HNSCC from 2001-2013 at our institution. The primary sites included oropharynx (n=735), oral cavity (OCC, n=182), larynx (n=180) and hypopharynx (n=50). Among patients who developed distant metastasis (DM), the the number of clinically or radiographically apparent tumors was assessed. Survival estimates following DM were generated using the Kaplan-Meier method and compared using log-rank testing. Cox proportional hazards models were used for univariate (UVA) and multivariate analyses (MVA). Results: A total of 148 (13%) patients developed DM at a median time of 10.7 months (range 0.3-81.2) after IMRT. The median follow-up time following DM was 48 months. 5-year survival following DM was significantly longer in patients with a solitary metastatic lesion compared to multiple lesions (table 1, p=0.001). Of the 19 patients with solitary metastasis, the 14 who received definitive local therapy with either surgery or radiation survived longer than those who did not (5-year survival 55.7% vs 0%, p=0.001), though patients who did not receive local therapy were of poorer performance status. On UVA and MVA, longer survival after DM was associated with presence of a solitary metastatic tumor (MVA hazard ratio 0.31, 95% CI 0.16-0.59, p=0.001). Conclusions: An oligometastatic phenotype characterizes HNSCC patients with solitary metastasis, especially when amenable to definitive local therapy. These findings have important implications regarding clinical trial design for HNSCC in the recurrent and oligometastatic setting. [Table: see text]

Survival outcomes for various treatment modalities in early-stage grade 3 follicular lymphoma (FL3): a National Cancer Database (NCDB) study.

7551 Background: The prognosis, response to therapy and curability of FL3 is controversial. 5-year Overall Survival (OS) in the literature ranges from 35-72% (Ganti 2006). The aim of this study was to compare the OS for patients with early-stage FL3 managed with single- and multi-agent chemotherapy (CT) with and without radiotherapy (RT). Methods: We identified patients (pts) diagnosed with stage I &amp; II FL3 between 2004 – 2012 from the NCDB and categorized into 3 groups based on therapy – pts given single agent CT with or without RT were combined due to small sample sizes (SA±RT), multi-agent CT without RT (MA-RT), and multi-agent CT with RT (MA+RT). We calculated OS for each group using Kaplan-Meier method and compared the results using Log Rank test. Cox regression model was used to identify factors which had significant impact on OS. Results: 1,563 pts were identified – 827 (53%) with stage I and 736 (47%) with stage II FL3. Median age was 61 yrs (range 18-90yrs); 750 (48%) males, 813 (52%) females; 1423 (91%) whites, 76 (5%) blacks. 112 (7%) received SA±RT, 886 (57%) MA-RT and 565 (37%) MA+RT. 5-year OS for MA+RT (95%) was significantly more than MA-RT (87%; HR 0.33, P&lt;0.001) or SA±RT (88%; HR 0.38, P=0.007). Cox regression indicated that age (HR 1.05, P&lt;0.001), sex (HR 0.66 for females, P=0.02), comorbidities (HR 1.60 for Charlson Deyo Score 1, P=0.04; HR 3.07 for Score 2, P=0.001), stage (HR 1.79, P=0.001), insurance status (HR 0.22 for insured, P&lt;0.001) and increasing year of diagnosis (HR 0.92, P=0.03) also had significant impact on OS. Median radiation dose for the MA+RT was 36Gy (interquartile range 30.6 – 36Gy), and the proportion of patients who received greater than 36Gy decreased from 55% in 2004 to 38% in 2012 and at the same time, the proportion of patients who received intensity modulated RT increased from 5% in 2004 to 15% in 2012. Use of MA CT declined (2004 95% v 2012 89%, P=0.02) but there was no significant trend in use of RT (2004 39% v 2012 34%) during the periods studied. Conclusions: For pts with early-stage FL3, there was an association of improved survival with the use of MA+RT over other treatment strategies and appear to have outcomes superior to what has been previously reported.

Effect of IMRT and three-dimensional conformal radiotherapy on oral Candida colonization: A comparative study

Aim: To investigate oral candidiasis in patients with head and neck cancer before and after intensity-modulated radiation therapy and three-dimensional conformal radiotherapy (3D CRT) and to explore if there is an association with the type of radiotherapy used and the severity of candidiasis. Materials and Methods: Patients who received radiation therapy (RT) for the treatment of head and neck cancer were divided into two groups: Group 1 consisted of patients (n = 20) who received Intensity modulated radiation therapy (IMRT) and Group 2 (n = 20) consisted of patients who received 3D CRT. Saliva from these patients was collected before and after radiotherapy and evaluated for Candida species using culture method. Results: Significant increase of Candida albicans was seen in patients who underwent 3D CRT as compared to IMRT. Other species of Candida such as Candida tropicalis, Candida glabrata, and Candida krusei showed increase postradiotherapy in both groups, but the change was not significant. Conclusion: Although candidiasis is seen regardless of the type of radiation therapy used, the oral environment is more stable after intensity-modulated radiation therapy as and when compared to 3D CRT. Salivary substitutes and good oral hygiene before, during, and after radiotherapy could be used to increase oral clearance and to decrease the chance of candidiasis.

Prophylactic use of pentoxifylline and tocopherol in patients undergoing dental extractions following radiotherapy for head and neck cancer

Background:In head and neck cancer patients undergoing radiotherapy, osteoradionecrosis (ORN) of the jaw is one of the major but uncommon complications. Satisfactorily results have been observed while treating ORN patients with upcoming treatment modalities such as combination therapy of pentoxifylline and Vitamin E (PVe). It is believed that in patients undergoing dental extractions, these treatment modalities can be used prophylactically for lowering the risk of development of ORN. Hence, keeping all these things in mind, we planned the present study to assess the prophylactic role of pentoxifylline and tocopherol in patients who require dental extractions after radiotherapy for cancer of head and neck.Materials and Methods:A total of 110 patients were included in this retrospective study, which had radiotherapy for cancer of the head and neck. After radiotherapy, a total of 450 dental extractions were done in these 110 patients.Results:External beam therapy was given in 92.72% of the patients. 7.27% and 40% of the patients received intensity modulated radiotherapy combination of chemotherapy and intensity modulated radiotherapy, respectively. ORN developed only in 2 patients. Patients had taken PVe for a mean of 12 (24) weeks preoperatively and 14 (18) weeks postoperatively. The incidence was lower than that normally associated with dental extractions in irradiated patients.Conclusion:In patients undergoing dental extractions, after receiving radiotherapy of head and neck region, combination therapy of pentoxifylline and tocopherol are sufficiently effective.

Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study

Toexplore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70Gy in 35 fractions over 7weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiationtherapy began within 15minutes after HBO. Patients were followed for2years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+years for local recurrence, distant metastases, disease-specific survival, and overall survival. Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5minutes, with 2 of 231 administrations delivered beyond 15minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO. While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.

Dose-Volume Correlates of Osteoradionecrosis of the Mandible in Oropharynx Patients Receiving Intensity Modulated Radiation Therapy

Dose-Volume Correlates of Osteoradionecrosis of the Mandible in Oropharynx Patients Receiving Intensity Modulated Radiation Therapy

Assessing feasibility, compliance and toxicity of concomitant chemo-radiotherapy in head and neck cancers in the Northern Territory: initial experience and challenges.

IntroductionComprehensive oncology services have recently been introduced in the Northern Territory (NT) enabling delivery of concurrent chemo‐radiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LAHNSC). The purpose of this study is to assess feasibility, compliance and toxicity of CCRT in remote Australia.MethodsChart review was conducted for all patients >18 years, with biopsy‐proven LAHNSC, receiving curative intent CCRT between January 2010 and September 2012.ResultsThe study population comprised of 26 patients, 20 Caucasian and 6 Indigenous, having a median age of 58 years, with most common sites of involvement being the oropharynx (n = 16) and the oral cavity (n = 6). Major risk factors were smoking and alcoholism. Cardiovascular disease, viral hepatitis, latent tuberculosis and strongyloidosis were the major comorbidities. Fifty‐eight per cent (n = 15) required assisted feeding. All patients received intensity modulated radiotherapy. Systemic therapy comprised of cisplatin or carboplatin/cetuximab. Most common acute (grade 3/4) toxicities were mucositis, dysphagia and dermatological in 54%, 31% and 23% respectively. Complications were infection and gastrostomy insertion related.Hospitalisation occurred in 23%, treatment break >2 days in 38%, with no difference in toxicities between indigenous and nonindigenous patients. Platinum use was associated with greater nausea (P = 0.003), renal dysfunction (P = 0.03) and ototoxicity (P = 0.04) and cetuximab with dermatological reactions (P = 0.05). At median follow‐up of 16 months, overall survival was 58% with progression‐free survival of 50%.ConclusionsWe have demonstrated good compliance rates, tolerance and feasibility outcomes. The seeming preponderance of LAHNSC in the NT is cause for concern.

Prospective MRI-based imaging study to assess feasibility of proton therapy for post-prostatectomy radiation

Purpose/Objectives: To optimize delivery of post-prostatectomy radiation (PPRT) with protons by examining dosimetric effects of variations in physician contouring, organ motion, and patient alignment during a course of PPRT. Material and methods: We enrolled 10 patients receiving PPRT in a prospective imaging study. All patients underwent combined computed tomography (CT)/magnetic resonance imaging (MRI) simulation with endorectal balloon (ERB) and received intensity modulated radiation therapy (IMRT) per institutional standards. Study patients underwent weekly MRI verification scans in the treatment position. Three radiation oncologists contoured clinical target volumes (CTV) on initial and verification scans using two consensus guidelines (RTOG and EORTC). We generated IMRT, double scattering (DS), and pencil beam scanning (PBS) proton plans and examined the dosimetric impact of contour variations, inter-fraction motion, and patient alignment techniques. Results: Inter-observer variations in contouring reduced median CTV coverage (D100) by 0.9% for IMRT plans, 2.8% for DS proton plans, 3.4–4.9% for PBS Proton Plans. Inter-fraction changes in target volumes due to internal organ motion resulted in a median loss of target dose coverage (D98) of 0% with IMRT, 3.5% with DS, and 8.1–8.3% with PBS. Median bladder V65Gy increased during the treatment course with all techniques (6.0–7.5%). Changes in the median rectal V60Gy remained small regardless of the treatment technique (0.5–3.1% increase). Alignment to the ERB after cranio-caudal bony alignment reduced CTV displacement compared to bony alignment alone, and as a result CTV coverage (D98) changed <2% with IMRT, DS, and PBS. Conclusion: Proton-based treatments are more sensitive to changes in inter-fraction organ motion during PPRT compared to IMRT, and therefore motion management and patient alignment methods are critical. Patient alignment using bony anatomy as well as the ERB minimizes displacement of the CTV, and reduces variation in target dose coverage particularly for PBS proton therapy.

DOSE-ESCALATED EXTERNAL BEAM RADIOTHERAPY DURING HORMONO-RADIOTHERAPY FOR PROSTATE CANCER

Introduction. The introduction of modern technologies of conformal external beam radiotherapy (EBRT) into clinical practice for the treatment of prostate cancer requires proper quality assurance measures as well as a careful analysis of both the efficacy and toxicity data of treatments. The purpose of this study was to inves- tigate tolerance and the immediate efficacy of conformal dose-escalated EBRT during hormono-radiotherapy for prostate cancer. material and methods. The study involved 156 prostate cancer patients treated with EBRT. Among them, 30 patients received a total dose of 70 Gy, and in 126 patients the total dose was esca- lated to 72-76 Gy (median total dose - 74.0 Gy). Fifty-nine patients received intensity modulated radiation therapy. Results. The prescribed course of treatment was completed in all the patients with prostate cancer. Acute radiation-induced bladder reactions (RTOG) were observed in 50 (32.1 %) patients, of whom 48 (30.8 %) experienced grade I reactions, and 2 (1.3 %) experienced grade II reactions. Eighteen (11.5 %) patients had radiation-induced rectum reactions, not above grade I. The development of grade II dysuric phenomena necessitated treatment interruption only in two patients. Of 9 (5.8 %) patients who had late bladder complica- tions (RTOG/EORTC), 8 (5.1 %) patients developed grade I complications, and one (0.6 %) patient developed grade II complications. Of 11 (7.1 %) patients who had rectum complications, 8 (5.1 %) patients developed grade I complications, and 3 (1.9 %) patients developed grade II complications. No patients experienced the increase in toxicity of treatment during dose escalation up to a total dose exceeding 70 Gy. During the follow-up period, only one patient developed recurrent disease. Conclusion. The results of our study suggest acceptable levels of toxicity following a continuous course of dose-escalated EBRT given in conjunction with hormono-radiotherapy to prostate cancer patients. Further studies are needed to investigate the impact of dose escalation on long-term outcomes as well as the rate and grade of late complications.

Radiation Pneumonitis Risk after Bleomycin Toxicity in Hodgkin Lymphoma Patients

Introduction:Combined modality treatment with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy followed by consolidative radiation to start within 3-4 weeks is the current accepted approach in the treatment of patients with early stage Hodgkin lymphoma (HL). Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in HL patients. We undertook this study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation in these patients.Methods:We reviewed the records of all HL patients treated with ABVD followed by radiation therapy (RT) to the chest between January 2009 and December 2014. We defined bleomycin toxicity as: the occurrence of clinical respiratory symptoms leading to discontinuation of bleomycin and/or bilateral opacities noted on computed tomography (CT) imaging and/or drop in diffusing capacity of the lung for carbon monoxide (DLCO) by 25%, in the absence of infection. We identified 129 patients, 100 of which received consolidation RT as part of combined modality and are the subject of this report, 29 patients were excluded because they developed relapse before getting RT. We compared patients with and without bleomycin toxicity for the following outcomes:•Frequency of RP using the Pearson chi-square test.•Interval between BPT and Radiation using Mann-Whitney U test (MWT)•Interval between end of chemotherapy and radiation using MWT.We used univariate Cox regression analysis to assess the risk of RP by looking at the time-interval in weeks from end of bleomycin to start of RT.Results:Median follow up was 23 months (6 - 69), Median age was 31 years (18-77), and 60% were females. Per our criteria, 28 patients developed BPT (25.5%). All patients received intensity modulated radiation therapy, radiation dose median was 30.60 Gy (20-42Gy). Mean lung dose (MLD) was a median of 9.4 Gy (2.6- 13.9 Gy). The median interval between chemotherapy and RT was 3 weeks (1- 8 weeks). Median interval from stopping bleomycin, either as a precaution or because of toxicity, to the start of RT was 5 weeks (1-20 weeks). Interval between documented bleomycin toxicity to start of radiation was a median of 8.5 weeks (2-20 weeks).We had 10 cases of RP (10%), 5 of which were ≥ Grade 2. There was no significant difference in RP risk in patients with or without BPT; 10.7% (3/28) versus 9.6% (7/72) respectively, P= 0.82.Patients with BPT versus those without BPT had no significant difference in baseline characteristics. The interval time from chemotherapy to radiation was a median of 3 weeks in both groups with or without BPT showing no difference; P= 0.83. However, Patients with BPT had a significantly longer interval from last bleomycin cycle to start of radiation compared to those without BPT (median 8.5 vs. 5 weeks, p =0.014).The intervals from chemotherapy to radiation treatment and from bleomycin to radiation treatment showed no significant correlation with RP on univariate Cox regression analysis (P= 0.41 and P= 0.12, respectively). This was maintained when adjusted for the number of bleomycin cycles.Treatment of BPTOf the 28 patients, 17 were managed by stopping bleomycin and observation only; 10 patients required a 2 week course of steroids. One patient went into severe respiratory compromise, was started on continuous oxygen and eventually recovered 48 hours later and went on to receive RT beginning 2 weeks after completing his steroid treatment. This patient did not have pulmonary complications after RT.All 28 BPT patients eventually completed their planned course of radiation. At last follow up, all 28 patients were alive and free of respiratory symptoms.Conclusion:In our cohort of Hodgkin lymphoma patients, those patients with bleomycin toxicity who received standard RT had no excess risk of subsequent RP. Moreover, patients were able to receive complete courses of RT to intended conventional radiation doses. Our findings suggest that RT does not need to be delayed following chemotherapy, except to allow for the completion of steroids or clinical recovery from BPT.Table 1BPT_clinicalBPT _imagingBPT_DLCO≥25%Clinical+(CTorDLCO≥25%)BPT per criteriaAll patients n=1002517101328RPNo n=90221591225Yes n=1032113 DisclosuresNo relevant conflicts of interest to declare.

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non Hodgkin Lymphoma

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non Hodgkin Lymphoma

Prospective Long-term Patient-Reported Quality of Life Outcomes Following Intensity Modulated Radiation Therapy in Head and Neck Cancer

Materials/Methods: Twenty-three patients without prior head and neck cancers or metastatic disease who were treated with PT to 70.0 Gy (RBE) (range, 61.2-74.4 Gy [RBE]) for major and minor salivary gland cancers were enrolled on an IRB-approved outcomes tracking protocol between 2006 and 2014. Twenty-one patients received postoperative PT and 2 received primary PT for unresectable disease. Gross residual disease was present in 7 patients at the time of PT. Five patients also received intensity modulated radiation therapy (median dose, 18 Gy; range, 16.2-50.4 Gy). Median follow-up was 2.5 years (range, 0.6-7.6 years). Grade 3 or higher toxicity was reported using the Common Terminology Criteria for Adverse Events, version 4. Results: The 3-year overall survival and disease-free survival rates were 81% and 73%, respectively. The 3-year local control, regional/neck control, and freedom from metastasis rates were 87%, 91%, and 81%, respectively. Gross residual disease was a major prognostic factor. The 3year local control, overall survival, and disease-free survival rates were 57%, 57%, and 29% for the 7 patients with gross disease, while for the remaining 16 patients who did not have gross disease at the time of PT, the 3-year local control, overall survival, and disease-free survival rates were 100% (PZ.0045), 92% (PZ.0136), and 94% (PZ.0003), respectively. Grade 3 toxicities occurred in 4 (17%) patients and included hearing loss, otitis externa with mastoiditis, double vision limiting activities of daily living, and a seizure secondary to radionecrosis. Median time after PT to grade 3 toxicity was 23 months. There were no grade 4 or 5 events. Conclusion: Proton therapy is an effective primary and postoperative therapy for salivary gland cancers. Nearly all patients who undergo gross total resection and proton therapy were cured. Unexpected serious toxicities were rare. The presence of gross disease at the time of proton therapy was the major negative prognostic factor. These patients are in need of innovative treatment strategies. Author Disclosure: T.L. Smith: None. C.M. Bryant: None. J.A. Bradley: None. D.J. Indelicato: None. C.G. Morris: None. R. Dagan: None.

SU‐E‐T‐317: Dosimetric Evaluation of Acuros XB Advanced Dose Calculation Algorithm in Head and Neck Patients

Purpose:The Acuros XB photon dose calculation algorithm is a newly implemented calculation technique within the Eclipse treatment planning system using deterministic solutions to the linear Boltzmann transport equations. The goal of this study is to assess the clinical impact of dose differences arising from a retrospective comparison of calculations performed using the Analytical Anisotropic Algorithm (AAA) and Acuros XB on patients.Methods:Ten head and neck patients receiving intensity modulated radiation therapy were selected as a pilot study. Initial evaluation was based on the percentage of the planning target volume (PTV) covered by the prescription dose, minimum dose within the PTV, and dose differences in critical structures. For patients receiving boost plans, dosimetric evaluations were performed on the plan sum of the primary and boost plans.Results:Among the ten patients there were a total of 21 PTVs corresponding to primary and boost volumes. Using the same normalization within Eclipse, the average percentage of the PTVs receiving the prescription dose were 95.6% for AAA and Acuros XB. The average minimum doses within the PTVs, expressed as a percentage of the prescription to the volume, were 82.3% and 83.6% for AAA and Acuros XB respectively. Neither comparison showed differences with statistical significance when subjected to a paired t‐test. Statistical significance was found in the average difference of the maximum dose for the mandible (242.5cGy, p=0.0005) and cord with a 5mm radial expansion (105.0cGy, p=0.0005) and in the median dose for the left parotid (25.0cGy, p=0.0423) and oral cavity (36.3cGy, p=0.002).Conclusion:The Acuros XB dose calculation algorithm did not exhibit significant differences in PTV coverage when compared to the AAA algorithm. Significant differences in critical structures are likely attributed to the structures proximity to high atomic number materials or air cavities, regions of known difficulty for the AAA algorithm.