Feasibility Of Dose Escalation Research Articles

Total Body Irradiation in the Era of New Radiotherapy Techniques

Total body irradiation (TBI), in combination with chemotherapy which is most often cyclophosphamide, is widely used since it was introduces in the fifties by E.D.Thomas as a preparatory regimen before bone marrow transplant. Even if it is an important part for conditioning regimen for patients with acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) undergoing hematopoietic stem cell transplantation, it is responsible for many side effects. New irradiation technique, tomotherapy and VMAT achieved a significant dose reduction to the OARs and the feasibility of dose escalation in a BMT conditioning regimen.

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma.

Background and purpose: Pediatric ependymoma carries a dismal prognosis, mainly owing to local relapse within RT fields. The current prospective European approach is to increase the radiation dose with a sequential hypofractionated stereotactic boost. In this study, we assessed the possibility of using a simultaneous integrated boost (SIB), comparing VMAT vs. IMPT dose delivery.Material and methods: The cohort included 101 patients. The dose to planning target volume (PTV59.4) was 59.4/1.8 Gy, and the dose to SIB volume (PTV67.6) was 67.6/2.05 Gy. Gross tumor volume (GTV) was defined as the tumor bed plus residual tumor, clinical target volume (CTV59.4) was GTV + 5 mm, and PTV59.4 was CTV59.4 + 3 mm. PTV67.6 was GTV+ 3 mm. After treatment plan optimization, quality indices and doses to target volume and organs at risk (OARs) were extracted and compared with the standard radiation doses that were actually delivered (median = 59.4 Gy [50.4 59.4]).Results: In most cases, the proton treatment resulted in higher quality indices (p < 0.001). Compared with the doses that were initially delivered, mean, and maximum doses to some OARs were no higher with SIB VMAT, and significantly lower with protons (p < 0.001). In the case of posterior fossa tumor, there was a lower dose to the brainstem with protons, in terms of V59 Gy, mean, and near-maximum (D2%) doses.Conclusion: Dose escalation with intensity-modulated proton or photon SIB is feasible in some patients. This approach could be considered for children with unresectable residue or post-operative FLAIR abnormalities, particularly if they have supratentorial tumors. It should not be considered for infratentorial tumors encasing the brainstem or extending to the medulla.

Results of a Prospective Dose Escalation Study of Linear Accelerator–Based Virtual Brachytherapy (BOOSTER) for Prostate Cancer; Virtual HDR Brachytherapy for Prostate Cancer

PurposeTo demonstrate feasibility and toxicity of linear accelerator–based stereotactic radiation therapy boost (SBRT) for prostate cancer, mimicking a high-dose-rate brachytherapy boost. Methods and MaterialsA phase 1 sequential dose escalation study of SBRT compared 20 Gy, 22 Gy, and 24 Gy to the prostate and 25 Gy, 27.5 Gy, and 30 Gy to the gross tumor volume in 2 fractions, combined with 46 Gy in 23 fractions of external beam radiation. Feasibility of dose escalation (volume receiving 125% and 150% of the dose) while meeting organ-at-risk dose constraints, grade 2 acute and late gastrointestinal and genitourinary toxicity, and freedom from biochemical failure were secondary endpoints. ResultsThirty-six men with intermediate- and high-risk prostate cancer were enrolled with a median follow-up of 24 months. Sixty-four percent of patients had high-risk features. Nine men were enrolled to dose level 1, 6 to level 2, and 6 to level 3. Another 15 patients were treated at dose level 3 on the continuation study. Dose level 3 achieved superior 125% (23.75 Gy) and 150% (28.5 Gy) dose compared to dose levels 1 and 2, with minimal differences in organ-at-risk doses. Kaplan-Meier estimate of freedom from biochemical failure at 3 years was 93.3%. There were no late grade 2 or 3 gastrointestinal events. The late grade 2 genitourinary toxicity at 2 years was 19.3%. Prostate-specific membrane antigen positron emission tomography was performed at 2 years with no local recurrences. ConclusionsWe have shown that a linear accelerator–based SBRT boost for prostate cancer is feasible and can achieve doses comparable to high-dose-rate boost up to the 150% isodose volumes. Rectal, bladder, and urethral doses remained low, and long-term toxicity was the same as or better than previous reports from high-dose-rate or low-dose-rate boost protocols.

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery

Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking. Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10-30Gy in 1 fraction to 0-5mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15-20Gy and 30Gy in 1 fraction marginal dose. For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30Gy to retrospective SRS plans to standard 15-20Gy and 30Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis. Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

Feasibility of Dose Escalation Using Intraoperative Radiotherapy Following Resection of Large Brain Metastases Compared to Post-Operative Stereotactic Radiosurgery

Dose reduction is used for increasing tumor volumes in stereotactic radiosurgery (SRS) due to risks of radiation injury reaction with increasing tumor diameter. This concept runs contrary to the general principles of oncology, where more tumor should not require less dose, and this may contribute to increases in local failure which approaches 40% in prospective studies for surgery followed by SRS. Thus alternative strategies are warranted. We hypothesize that the steep conformal fall off inherent to intra-operative radiotherapy (IORT) will afford dose escalation over SRS without increasing dose to critical structures.

EP-2232: Feasibility of dose escalation with individualised bladder filling for intrauterine brachytherapy

EP-2232: Feasibility of dose escalation with individualised bladder filling for intrauterine brachytherapy

The Feasibility of Dose Escalation With Simultaneous Integrated Boost (SIB) Technique in Patients With Large Functioning Pituitary Macroadenomas Treated With Robotic Radiosurgery

The Feasibility of Dose Escalation With Simultaneous Integrated Boost (SIB) Technique in Patients With Large Functioning Pituitary Macroadenomas Treated With Robotic Radiosurgery

Dosimetric Comparison of Volumetric Modulated Arc Therapy, Tomotherapy and Intensity Modulated Radiation Therapy for Radiation Dose Escalation of Hepatic Malignancies

Previously, radiation therapy has had a limited role in the management of hepatic malignancies due to the risk of radiation induced liver disease (RILD). However, recent advancements have allowed for dose escalation within the tumour volume while sparing normal tissues. These techniques have been employed, although comparisons regarding dosimetric integrity and the feasibility of dose escalation using normal tissue complication probability (NTCP) models have yet to be established. The aim of this study is to provide a dosimetric comparison of intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and Tomotherapy (HT) with regards to dose escalation for primary and metastatic hepatic malignancies. Seventeen clinically delivered IMRT plans and two clinically delivered VMAT plans for patients treated for liver cancer were retrospectively reviewed. Each data set was optimized using two alternate delivery techniques, providing each patient with an IMRT, VMAT and HT plan. The gross tumour volume (GTV) was defined by the original treating oncologist, no clinical target volume (CTV) was included and planning target volumes (PTV) were 3mm expansions. The dose prescription was escalated until an NTCP of 5% was exceeded or until dose-volume constraints of all other normal tissues, normalized to 2Gy equivalent biological effective dose (BED), was exceeded. All plans achieved intended normal tissue constraints, including dose to the normal liver. Mean doses for VMAT, HT and IMRT were 85.2±44.6Gy, 79.1±47Gy, and 72.4±41.5Gy, respectively. Analysis revealed statistical significance between escalation levels when comparing the three modalities to one another; VMAT vs. HT (p=<0.001), VMAT vs. IMRT (p<0.001), HT vs. IMRT (p=0.005). In four cases, dose escalations were limited by normal tissues, rather than 5% NTCP. A comparison between treatment times revealed significantly lower times for VMAT (149±42s) than HT (841±317s) (p<0.001). Analysis of monitor units (MU) for VMAT and IMRT depicted mean values of 1479±497MU and 1326±605MU, respectively (p=0.054). The utilization of partial arcs, coupled with the implementation of gating techniques allows VMAT to greatly reduce normal liver dose while achieving a high dose to the target volume. Overall, VMAT is superior in terms of dose escalation maximums and reduced treatment delivery time for hepatic cancer.

Initial Safety and Feasibility of Dose Escalation Using a Simultaneous Integrated Boost in Patients With Locally Advanced Gynecologic Malignancies

Initial Safety and Feasibility of Dose Escalation Using a Simultaneous Integrated Boost in Patients With Locally Advanced Gynecologic Malignancies

SU-E-T-814: Dosimetric Feasibility of Dose Escalation with Gated IG-IMRT for Pancreatic Cancer

Purpose: Delivery of curative high dose to the pancreatic tumor is limited by the surrounding radiation sensitive organs at risk (OARs), especially the most dose‐limitingorgan duodenum. Image‐guidedradiotherapy(IGRT) allows small planning target volume (PTV) margin and intensity‐modulated RT (IMRT) offers sharp dose gradients, permitting dose escalation with minimal OAR damage. We study the dosiemtric feasibility for using IG‐IMRT to escalate dose to pancreatic cancer. Methods: Planning 4D CT datasets for 10 pancreatic cancer patients treated previously were used for evaluation. A PTV margin of 3 mm was added to the clinical target volume (CTV, pancreatic head). This small margin is justified because the patient is to be treated with (1) gating to reduce the intrafractional (respiration) motion below 3 mm, and (2) high quality CT guided repositioning using an in‐room CT (e.g., CTVision, Siemens) to minimize interfractional variations. IMRT plans with prescription doses of 50.4 Gy and 72 Gy in 1.8 Gy fractions were generated using a planning system (Panther, Prowess). Results: A series of dose volume quantities at two prescription doses 50.4 and 72 Gy were compared. For six out of 10 patients, the duodenum volumes irradiated by at least 50.4 Gy (V50.4 Gy) with the prescription dose of 72 Gy are well below 50%, while the doses to other OARs are within the acceptable ranges. for two (seven) out of 10 patients the volumes irradiated by at least the prescription dose of 72 Gy are less than 5 (10) cc. Conclusions: With appropriate selection of patients with pancreatic cancer, the dose escalation to 72 Gy may be feasible by using gated IMRT with daily in‐room CT guidance.

Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma

To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy. Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F(45 Gy)) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT(50.4 Gy)) or 54 Gy (IMRT(54 Gy)) to the planning tumor volume. All plans were normalized so that > or =97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans. The mean volume of bowel receiving > or =45 Gy was lower with the IMRT(50.4 Gy) (33% lower) and IMRT(54 Gy) (18% lower) plans than with the 4F(45 Gy) plan. The mean volume of rectum receiving > or =45 Gy or > or =50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT(50.4 Gy) and IMRT(54 Gy) plans compared with the 4F(45 Gy) plan. Compared with the 4F(45 Gy) plan, the IMRT(50.4 Gy) plan resulted in a smaller volume of bowel receiving 35-45 Gy and a larger volume of bowel receiving 50-55 Gy. Compared with the 4F(45 Gy) plan, the IMRT(54 Gy) plan resulted in smaller volumes of bowel receiving 45-50 Gy; however, small volumes of bowel received 55-60 Gy with the IMRT plan. Intensity-modulated RT may permit an increase in the radiation dose that can safely be delivered to the central pelvis and pelvic lymph nodes after hysterectomy. However, dose-volume calculations using individual CT scans do not account for internal organ motion. Detailed data concerning the relationships among radiation dose, treatment volume, and treatment effects are lacking, and prospective studies of pelvic IMRT are needed to determine the safety and efficacy of this treatment.

The feasibility of dose escalation using concurrent radiation and 5-fluorouracil therapy following pancreaticoduodenectomy for pancreatic carcinoma

We evaluated the feasibility of dose escalation using external beam radiation therapy (RT) and 5-fluorouracil (5-FU) following pancreaticoduodenectomy for pancreatic carcinoma. Fourteen patients who underwent pancreaticoduodenectomy for stage I-III adenocarcinoma of the pancreas received postoperative high-dose chemoradiation. RT was given at 1.8-Gy daily fractions to total doses of 54 Gy for patients with negative surgical margins (n = 12), and 64.8 Gy for those with gross residual disease (n = 2). Concurrent 5-FU was given as a continuous infusion (CI) at 225 mg/m2 per day (n = 9) beginning or day 1 and continuing until the completion of RT, or by bolus injection at 500 mg/m2 per day (n = 5) during weeks 1 and 4 of RT. Follow-up ranged from 32 to 36 months (median, 35 months). All patients were able to complete the planned high-dose postoperative chemoradiation and none required a treatment break. No grade 4 acute toxicity was observed. Grade 3 acute toxicity was limited to 2 patients. Two patients developed grade 3 (n = 1) or 4 (n = 1) subacute toxicity, all gastrointestinal-related. There have been no fatal toxicities and no grade 3 or 4 late toxicity has been observed. The 3-year survival is 21%. Dose escalation of postoperative 5-FU chemoradiation following pancreaticoduodenectomy for pancreatic carcinoma is well tolerated. Further dose-intensification of postoperative adjuvant therapy in these patients appears feasible and is being evaluated in a recently activated national trial.

Experience with dose escalation using CHARTWEL (continuous hyperfractionated accelerated radiotherapy weekend less) in non-small-cell lung cancer

Results from the multicentre randomized trial of CHART (continuous, hyperfractionated, accelerated radiotherapy) in non-small-cell lung cancer (NSCLC) showed a significant increase in survival (P=0.004) compared with conventional radiotherapy and a therapeutic benefit relative to late radiation-induced morbidity. However, 60% of patients died because of failure to control locoregional disease. These findings have stimulated interest in assessing the feasibility of dose escalation using a modified CHART schedule. Acute and late morbidity with a CHARTWEL (CHART WeekEnd Less) schedule of 54 Gy in 16 days was compared with that observed with 60 Gy in 18 days in patients with locally advanced NSCLC. The incidence and severity of dysphagia and of analgesia were scored using a semiquantitative clinical scale. Late radiation-induced morbidity, namely pulmonary, spinal cord and oesophageal strictures, were monitored using clinical and/or radiological criteria. Acute dysphagia and the analgesia required to control the symptoms were more severe and lasted longer in patients treated with CHARTWEL 60 Gy (P< or = 0.02). However, at 12 weeks, oesophagitis was similar to that seen with 54 Gy and did not lead to consequential damage. Early radiation pneumonitis was not increased but, after 6 months, there was a higher incidence of mild pulmonary toxicity compared with CHARTWEL 54 Gy. No cases of radiation myelitis, oesophageal strictures or of grade 2 or 3 lung morbidity have been encountered. CHARTWEL 60 Gy resulted in an enhancement of oesophagitis and grade 1 lung toxicity compared with CHARTWEL 54 Gy. These were of no clinical significance, but may be important if CHARTWEL is used with concomitant chemotherapy. These results provide a basis for further dose escalation or the introduction of concurrent chemotherapy.