IMRT Era Research Articles

Comparison of the Clinical Behaviour of N3 HPV Related and Unrelated Head and Neck Cancer in the IMRT Era

Comparison of the Clinical Behaviour of N3 HPV Related and Unrelated Head and Neck Cancer in the IMRT Era

Outcome and Toxicity of Hypofractionated Conformal Radiation Therapy (HCRT) in Early Glottis Cancer: A Baseline for Comparison in the IMRT Era

We report the survival and toxicity outcomes in a population based cohort of patients treated with HCRT in a teaching institution. We retrospectively reviewed consecutive patients with T1-T2 glottic cancer seen between January 2006 to January 2013. 89%, received 52.5 Gy in 20 fractions over 4 weeks. 82%, were treated with 6MV photons and 18% with Cobalt. Patient information was collected and stored in our head and neck registry database. Descriptive statistics were calculated for all relevant demographic variables. Overall survival and relapse free survival was estimated using a Kaplan-Meier method. Cumulative incidence of second malignancy was calculated; death was a competing risk. Toxicity was defined as adverse effects present during and following treatment. A total of 114 patients were evaluated. Median follow-up was 4.6 years. Overall survival at 1, 2, 3, 4 and 5 years were 98, 96, 91, 88 and 83%. Relapse-free survival rates at 1, 2, 3, 4 and 5 years were 91, 90, 88, 85 and 85%. In total, 16 patients relapsed; 12 locally, 3 in regional lymph nodes and 1 with distant metastases. Mean time to relapse was 17.3 months Toxicity: Odynophagia was present in 97% at end of RT (58% severe), 23% at 1 month and 4% at 3 months post-RT. Xerostomia was present in 56% of patients at the end of RT, 25% at 1 month and 19% at 3 months and 12% 6 months and longer. A total of 86% developed dysguesia during RT. A total of 66% developed laryngeal mucositis by the end of RT. Dysphagia occurred in 49%, 18%, 8% and 6% of patients at end of RT, 1 and 3 and beyond 6 months respectively. Skin reaction was noted in 97% of patients, 65% had erythema, 15% had dry desquamation and 16% had moist desquamation at end of RT. A total of 71% had no skin reaction at 1-month post-RT. Mild laryngeal edema was noted in 42% and persisted in 16% of patients beyond 3 months. Hoarse voice was noted at the end of RT in all patients, this decreased to 88% at 1 month, 70% at 3 months and 59% at 6 months. Voice quality recovered completely in 53%, improved mildly for 13%, and worsened in only 1%. Telangiectasia was noted in 60% of patients, of which 90% were noted along the laryngeal mucosa, 3% along skin surface and 3% on both skin and mucosa. Of 52 evaluated patients, 34 remained euthyroid, 2 were hypothyroid prior to RT, 6 developed hypothyroidism post-RT and 10 post salvage surgery. Second malignancies were identified in 21 of 114 (18%) patients and included bladder (2), CLL (1), colorectal (3), lung (9), prostate (3), and non-melanoma skin cancer (3). None were in-field and median time to second malignancy was 2.1 years, with cumulative incidence of developing second cancer of 17.3% (95% CI 0.100-0.264) at 5 years. Our survival and relapse rates are comparable to that in the literature. In the absence of randomized controlled trials, Our reported Radiation induced side effects could serve as a baseline in comparison to new approaches. It remains to be seen whether IMRT could further improve outcome and reduce toxicity. HCRT remains an excellent treatment option for early laryngeal cancer.

Investigating Semi-Quantitative In Vivo Spatial and Dosimetric Analytical Algorithms to Report GBM Patterns of Failures Following Chemoradiation in the IMRT Era

Investigating Semi-Quantitative In Vivo Spatial and Dosimetric Analytical Algorithms to Report GBM Patterns of Failures Following Chemoradiation in the IMRT Era

Outcomes and Prognostic Factors of Locally Recurrent Nasopharyngeal Carcinoma Receiving Salvage Re-irradiation in the IMRT Era

Outcomes and Prognostic Factors of Locally Recurrent Nasopharyngeal Carcinoma Receiving Salvage Re-irradiation in the IMRT Era

Dosimetric analysis and comparison of reduced longitudinal cranial margins of VMAT-IMRT of rectal cancer

BackgroundThe cranial border of the target volume (TV) in rectal cancer patients treated with neoadjuvant chemoradiation (nCRT) is mostly defined at the level of L5/S1. However, current studies have shown that relapse cranially of the target volume after neoadjuvant nCRT and surgery is very rare. A reduction of cranial TV margins could be reasonable to reduce toxicity to the organs at risk (OAR). In this study we compared the dose distribution to the OAR for different cranial longitudinal margins using a dose-volume histogram (DVH) analysis.MethodsTen patients with loco regional advanced rectal cancer were analysed retrospectively. All patients were planned for Volumetric Arc Therapy Radiation Therapy (VMAT). Next to the original PTV (PTV0), three new planning target volumes (PTV) were defined for each patient: The PTV0 reduced by 1 cm, 2 cm and 3 cm on cranial extension. For each PTV a treatment plan with a total dose of 50.4 Gy with daily doses of 1.8 Gy was calculated. Dose to the OAR were evaluated and compared.ResultsFor the bone marrow, the small bowel and the peritoneal space all clinically relevant relative dose parameters (V10-V50) as well as the Dmedian could be significantly reduced with every cranial target volume reduction of 1 cm. For V10 of the peritoneal space the dose could be nearly halved with a 3 cm shortened TV. After TV reduction of 3 cm also for the urinary bladder a significant dose reduction of the Dmedian could be achieved.ConclusionsConsidering the very low recurrence rates in the TME and IMRT era, the distribution patterns of these relapses as well as the relevant side effects of nCRT, we would agree with existing recommendations of reduction of the cranial target volume in nCRT treated rectal cancer patients.

A Prospective Study of the Tolerance Dose of the Brain Stem in the IMRT Era

A Prospective Study of the Tolerance Dose of the Brain Stem in the IMRT Era

Dose-volume correlates of mandibular osteoradionecrosis in Oropharynx cancer patients receiving intensity-modulated radiotherapy: Results from a case-matched comparison

PurposeTo determine dosimetric parameters associated with osteoradionecrosis (ORN) in oropharyngeal cancer (OPC) patients in the IMRT era. Material and methodsSubsequent to institutional review board approval, we identified ORN in OPC patients treated with IMRT from 2002 to 2013. 1:2 case-control matching was implemented. Mandibular dose-volume histograms (DVH) were extracted. Dosimetric parameters were compared using non-parametric stats. Recursive partitioning analysis (RPA) was done to identify DVH correlates of ORN. Results68 ORN cases and 131 controls were matched. Median follow-up was 41months and median time to development of ORN was 16months. Mandibular mean dose was significantly higher in the ORN cohort (48.1 vs 43.6Gy, p<0.0001). However, the maximum dose was not statistically different. DVH bins from V35 to V73 were all significantly higher in the ORN cohort compared with controls (p<0.0006). Two DVH parameters were identified in RPA analysis, V43 and V58. The majority (81%) of ORN cases were observed with both V44≥42% and V58≥25%. ConclusionsOur data demonstrate that a wide range of DVH parameters in the intermediate and high beam path were all significantly higher in ORN patients. Mandibular V44<42% and V58<25% represent reasonable DVH constraints for IMRT plan acceptability, when tumor coverage is not compromised.

SU‐F‐T‐279: Impact of Beam Energy Drifts On IMRT Delivery Accuracy

Purpose:According to TG‐40 percent‐depth‐dose (PDD) tolerance is ±2% but TG‐142 is ±1%. Now the question is, which one is relevant in IMRT era? The primary objective of this study is to evaluate dosimetric impact of beam‐energy‐drifts on IMRT‐delivery.Methods:Beam‐energy drifts were simulated by adjusting Linac's bending‐magnet‐current (BMC) followed by tuning the pulse‐forming network and adjusting gun‐current. PDD change of −0.6% and +1.2% were tested. Planar‐dosimetry measurements were performed using an ionization‐chamber‐array in solid‐water phantoms. Study includes 10‐head‐and‐neck and 3‐breast cancer patients. en‐face beam‐deliveries were also tested at 1.3cm and 5.3cm depths. Composite and single‐field dose‐distributions were compared against the plans to determine %Gamma pass‐rates (%GPRs). For plan dose comparisons, changes in %Gamma pass‐rates (cPGPRs) were computed/reported to exclude the differences between dose‐computation and delivery. Dose distributions of the drifted‐energies were compared against their baseline measurements to determine the% GPRs. A Gamma criteria of 3%/3mm was considered for plan‐dose comparisons while 3%/1mm used for measured dose intercomparisons.Results:For composite‐dose delivery, average cPGPRs were 0.41%±2.48% and −2.54%±3.65% for low‐energy (LE) and high‐energy (HE) drifts, respectively. For measured dose inter‐comparisons, the average%GPRs were 98.4%±2.2% (LE‐drift) and 95.8%±4.0 (HE‐drift). The average %GPR of 92.6%±4.3% was noted for the worst‐case scenario comparing LE‐drift to HE‐drift. All en‐face beams at 5.3 cm depth have cPGPRs within ±4% of the baseline‐energy measurements. However, greater variations were noted for 1.3cm depth. Average %GPRs for drifted energies were &gt;99% at 5.3cm and &gt;97% at 1.3cm depths. However, for the worst‐case scenario (LE‐drift to HE‐drift) these numbers dropped to 95.2% at 5.3cm and 93.1% at 1.3cm depths.Conclusion:The dosimetric impact of beam‐energy drifts was found to be within clinically acceptable tolerance. However, this study includes a single energy with limited range of PDD change. Further studies are on going and the results will be presented.Received funding from Varian Medical Systems, Palo Alto, CA

The dosimetric impact of target volume delineation variation for cervical cancer radiotherapy

BackgroundCervical cancer inter-observer delineation variation has been demonstrated. This article addresses its dosimetric impact. Methods21 centres outlined two INTERLACE trial quality assurance test cases. A gold standard clinical target volume (GSCTV) was created from a consensus and STAPLE outline. RapidArc plans were created for all centres’ planning target volumes (PTVs; PTV1+2). Gold standard PTVs (GSPTVs) were created for each plan by applying each centre’s CTV–PTV margins to GSCTV. DVH parameters including D95% and Dmean for each PTV1+2 and GSPTV were compared, representing planned versus GSPTV delivered dose. PTV1+2 and GSPTV V95% was also calculated. ResultsReviewing all parameters, no plans achieved acceptable GSPTV coverage. GSPTV V95%⩾95% was not achieved for any plan. GSPTV V95%<90% in 15/21 (case 1) and 14/22 (case 2) and <80% in 2 plans from both cases. GSPTV V95% is on average 10–15% lower than planned and GSPTV D95% is 10–20% lower than planned. Most common GSCTV anatomical areas not receiving 95% dose were vagina, obturator and external iliac nodes and, in case 1, the superior nodal aspect. ConclusionCervical cancer CTV delineation variation leads to significant reductions in dose delivered to GSPTV. This highlights the ongoing importance of standardising delineation in the IMRT era.

Risk profile for osteoradionecrosis of the mandible in the IMRT era.

BackgroundThe risk for osteoradionecrosis (ORN) of the mandible is positively related to bone volume exposed to > ~ 60 Gy. We hypothesized that in combined treatment, surgery may also be a risk factor.Patients and methodsThe impact of mandibular surgery on ORN in locally disease-free IMRT cohorts was retrospectively analyzed.ResultsBetween October 2002 and October 2013, 531 of 715 patients with oral cavity cancer (OCC), mesopharyngeal cancer (MC), or salivary gland tumor were treated with the mandible bone exposed to ~ > 60 Gy (mean follow-up, 38 months; 7–143 months). Of the 531 patients, 36 developed ORN (7 %; 1.5 % with grade 3–4). The ORN rate in definitive IMRT MC (16/227) and in postoperative IMRT OCC patients with no mandibular surgery (3/46) was 7 % each; in OCC patients with mandibular surgery the rate was 29 % (15/60, p = 0.002). Marginal or periosteal bone resection was found to be a high risk factor (39 %, vs. 7 % followed by segmental or no resection, p < 0.0001).ConclusionMarginal or periosteal bone resection of the mandible was identified as the highest ORN risk factor in our IMRT cohort.

SU‐E‐J‐206: Adaptive Radiotherapy for Gynecological Malignancies with MRIGuided Cobolt‐60 Radiotherapy

Purpose:Even in the IMRT era, bowel toxicity and bone marrow irradiation remain concerns with pelvic irradiation. We examine the potential gain from an adaptive radiotherapy workflow for post‐operative gynecological patients treated to pelvic targets including lymph nodes using MRI‐guided Co‐60 radiation therapy.Methods:An adaptive workflow was developed with the intent of minimizing time overhead of adaptive planning. A pilot study was performed using retrospectively analyzed images from one patient's treatment. The patient's treated plan was created using conventional PTV margins. Adaptive treatment was simulated on the patient's first three fractions. The daily PTV was created by removing non‐target tissue, including bone, muscle and bowel, from the initial PTV based on the daily MRI. The number of beams, beam angles, and optimization parameters were kept constant, and the plan was re‐optimized. Normal tissue contours were not adjusted for the re‐optimization, but were adjusted for evaluation of plan quality. Plan quality was evaluated based on PTV coverage and normal tissue DVH points per treatment protocol. Bowel was contoured as the entire bowel bag per protocol at our institution. Pelvic bone marrow was contoured per RTOG protocol 1203.Results:For the clinically treated plan, the volume of bowel receiving 45 Gy was 380 cc, 53% of the rectum received 30 Gy, 35% of the bladder received 45 Gy, and 28% of the pelvic bone marrow received 40 Gy. For the adaptive plans, the volume of bowel receiving 45 Gy was 175–201 cc, 55–62% of the rectum received 30 Gy, 21– 27% of the bladder received 45 Gy, and 13–17% of the pelvic bone marrow received 40 Gy.Conclusion:Adaptive planning led to a large reduction of bowel and bone marrow dose in this pilot study. Further study of on‐line adaptive techniques for the radiotherapy of pelvic lymph nodes is warranted.Dr. Low is a member of the scientific advisory board of ViewRay, Inc.

Refinement and Individualization of Clinical Target Volume Delineation in Nasopharyngeal Carcinoma: A 22-Year Clinical Experience

Radiation-related toxicity in nasopharyngeal carcinoma (NPC) is common, even in the IMRT era. Little progress has been made on the refinement of target volume delineation. There is no well-established guideline for clinical target volume (CTV) delineation. A common practice is to add a fixed circumferential margin around gross tumor volume (GTV). Another common practice is to routinely include certain bony structures such as the posterior third of the maxillary sinus/nasal cavity and sphenoid sinus, irrespective of tumor extent, an approach that was used to define field borders in the 2D era.

Modeling Clinical Radiation Responses in the IMRT Era

The purpose of this review is to highlight the critical issues of radiobiological models, particularly as they apply to clinical radiation therapy. Developing models of radiation responses has a long history that continues to the present time. Many different models have been proposed, but in the field of radiation oncology, the linear-quadratic (LQ) model has had the most impact on the design of treatment protocols. Questions have been raised as to the value of the LQ model given that the biological assumption underlying it has been challenged by molecular analyses of cell and tissue responses to radiation. There are also questions as to use of the LQ model for hypofractionation, especially for high dose treatments using a single fraction. While the LQ model might over-estimate the effects of large radiation dose fractions, there is insufficient information to fully justify the adoption of alternative models. However, there is increasing evidence in the literature that non-targeted and other indirect effects of radiation sometimes produce substantial deviations from LQ-like dose-response curves. As preclinical and clinical hypofractionation studies accumulate, new or refined dose-response models that incorporate high-dose/fraction non-targeted and indirect effects may be required, but for now the LQ model remains a simple, useful tool to guide the design of treatment protocols.

Evolution of treatment for nasopharyngeal cancer – Success and setback in the intensity-modulated radiotherapy era

Background and purposeTo assess the therapeutic gains and setbacks as we evolved from the 2-dimensional radiotherapy (2DRT) to conformal 3-dimensional (3DRT) and to intensity-modulated (IMRT) era. Materials and methods1593 consecutive patients from 1994 to 2010 were retrospectively analyzed. Evolving changes in the different era included advances in staging investigation, radiotherapy technique, dose escalation, and use of chemotherapy. ResultsThe 3DRT era achieved significant improvement in local failure-free rate (L-FFR), disease-specific survival (DSS) and overall survival (OS). Neurological damage and bone/soft tissue necrosis were significantly reduced. However, the improvement in distant failure-free rate (D-FFR) was insignificant, and more hearing impairment occurred due to chemotherapy. Significantly higher D-FFR was achieved in the IMRT era, but L-FFR did not show further improvement. 5-Year DSS increased from 78% in the 2DRT, to 81% in the 3DRT, and 85% in the IMRT era, while the corresponding neurological toxicity rate decreased from 7.4% to 3.5% and 1.8%. ConclusionsSignificant improvement in survival and reduction of serious toxicity was achieved as we evolved from 2DRT to 3DRT and IMRT era; the therapeutic ratio for all T-categories improved with more conformal techniques. Improvements in tumor control were attributed not only to advances in RT technique, but also to better imaging and increasing use of potent chemotherapy. However, it should also be noted that hearing impairment significantly increased due to chemotherapy, L-FFR reached a plateau in the 3DRT era, and it is worrisome that the result for T4 remained unsatisfactory. Besides exploring for more potent chemotherapy and innovative methods, the guideline on dose constraint should be re-visited to optimize the therapeutic ratio.

Preoperative chemoradiotherapy for pancreatic cancer encountered vertebral compression fractures.

227 Background: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer at our institute achieved excellent cure rates, while treated patients encountered vertebral compression fractures (VCFs) frequently. Methods: From January 2006 to December 2011, 220 patients (male/female: 134/86, median age: 66 (range: 33-84)) with resectable pancreatic cancer have been treated with preoperative CRT with GEM. This method consisted of concurrent radiotherapy (50-60 Gy in 25 fractions over 5 weeks) and chemotherapy (GEM 1,000 mg/m2intravenous, weekly for 12-15 weeks, 3 times during 4 weeks). Three-dimensional conformal radiotherapy was used and its fields covered both primary pancreatic tumor and retropancreatic tissues with 50 Gy level. Boost irradiation to the roots of celiac and superior mesenteric arteries with 2.4 Gy/fr using field-within-field technique has been started since 2009. The risk factors for VCF and its causes were retrospectively analyzed for 1,308 Th10-L3 vertebral bodies. Results: Follow-up time from the initiation of CRT ranged from 3.4-73.9 months (median: 17.9). Median overall survival time of these patients was 40.6 months. Radical surgery was completed in 164 patients (75%). Twenty-five patients (11%) diagnosed as VCF (CTCAE v4.0 grade1/2: 12/13) and 22 of them were at 3.6-23 months from CRT. Cumulative incidence rates at 2 years were 18.9% in total, 8.5% in male and 38.4% in female (p = 0.0002). Corresponding rates were 5.1% in age &lt; 60 and 24.9% in age ≥ 60 (p = 0.0107). On their courses 37 de novo VCFs (Th10/11/12/L1/2/3: 2/3/11/13/7/1) were observed at first and 9 patients repeated VCFs near the initial VCFs. Dose-volume factors of each vertebral bodies also significantly correlated with VCF; vertebrae whose mean dose were &lt; 38 Gy/ ≥ 38 Gy developed VCFs in 2.7%/10.0% at 2 years (p &lt; 0.0001), vertebrae whose V30 were &lt; 80%/≥80% developed VCFs in 2.4%/10.6% (p &lt; 0.0001). Conclusions: Besides women and higher age, dose-volume factors of radiotherapy were risk of developing VCF in patients with pancreatic cancer after preoperative CRT with GEM. These findings should be considered to avoid VCFs as late adverse event after CRT for pancreatic cancer, especially in IMRT era.

Trends in Radiation Oncology Services in the IMRT Era: Evolving Patterns of Usage and Payments in Medicare Patients from 2000-2009

Trends in Radiation Oncology Services in the IMRT Era: Evolving Patterns of Usage and Payments in Medicare Patients from 2000-2009

Temporal lobe necrosis: a dwindling entity in a patient with nasopharyngeal cancer after radiation therapy

IntroductionOur objective was to report a case of misdiagnosed temporal lobe necrosis (TLN) in a patient with nasopharyngeal cancer (NPC) after radiation therapy.Case PresentationWe report a case of a 45 years old Chinese woman who developed moderate to severe headache and dizziness 1 year after 2D radiation therapy for NPC. Subsequent MRI scanning revealed a big enhancing mass in the right temporal lobe. The initial diagnosis was metastatic or intracranial extension of NPC, or a primary intracranial malignancy. She was referred to the neurosurgery department where a maximal surgical resection of the lesion was performed. A diagnosis of TLN was made according to the final histology.ConclusionTLN still matters in the IMRT era. The diagnostic quagmire of TLN lies in its close resemblance to neoplasm on clinical presentation and imaging. Reviewing the patient's treatment plan to scrutinize the dose to the temporal lobes is an important prerequisite for diagnosis.

Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma and Anaplastic Astrocytoma: Validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) in the IMRT and Temozolomide Era

Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma and Anaplastic Astrocytoma: Validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) in the IMRT and Temozolomide Era

13 Sites of neck failure in relation to midline cord shielding in nasopharyngeal carcinoma: Analysis in the IMRT Era

13 Sites of neck failure in relation to midline cord shielding in nasopharyngeal carcinoma: Analysis in the IMRT Era

An assessment of Biologically-based Optimization (BORT) in the IMRT era

The purpose of this study was to investigate the role of biological-based IMRT (BORT) in treatment planning development; more specifically, to assess the possible advantages of BORT over the classic 3-dimensional conformal radiation therapy (3DRT) and dose-based IMRT based on quantitative and qualitative indices. Three clinical cases are presented to evaluate the differences of BORT, IMRT, and 3DRT. 3DRT, IMRT, and BORT plans were generated for each case using a commercially available treatment planning system (Pinnacle by Philips). The plans were compared by evaluating biological endpoints such as tumor control probability (TCP), normal tissue control probability (NTCP), and uncomplicated tumor control probability (P+), as well as isodose line distribution, dose-volume histograms (DVHs), and dose uniformity. In all cases of this study, BORT yielded improved isodose coverage and P+. Our preliminary results suggest that BORT could play an important role in treatment planning optimization, especially as biological models and predictive assays become more accurate. Further case studies are needed to establish a definitive role for this type of optimization.