Clinical safety and efficacy of salvage reirradiation for upper abdominal malignancies.

PURPOSE: Reirradiation has the potential to provide effective local control of upper abdominal malignancies. This study aimed to evaluate the safety and efficacy of reirradiation for upper abdominal malignancies. METHODS: A total of 42 patients with a history of prior radiotherapy (RT) received reirradiation for abdominal malignancies between 2005 and 2017. Each patient's medical records, contours, and dose distribution for both RT courses were reviewed. The median dose of the prior RT was 50.0 Gy (range, 30.0-60.0 Gy) and the median dose of reirradiation was 45.0 Gy (range, 15.0-75.0 Gy). RESULTS: With a median follow-up of 10.9 months, the median infield-failure-free survival (IFFS) rate was 9.2 months. Gross tumor volume (GTV) significantly related to IFFS in both the univariate (p = 0.009) and multivariate analyses (p = 0.024), and patients with a GTV of <60.0 mL had an improved IFFS (p = 0.001). Four patients experienced ≥grade 3 late toxicities. In the retrospective dose reconstruction analysis in these patients, the cumulative dose to the most exposed 2 cc (D2cc) of the duodenum was >60.0 Gy (range, 60.1-73.7 Gy). In the univariate analysis, the D2cc of the duodenum and a preexisting duodenal ulcer identified using endoscopy prior to reirradiation significantly correlated with late severe toxicity (p = 0.021 and 0.017, respectively). CONCLUSIONS: Reirradiation for upper abdominal malignancies could be safely performed for patients without preexisting gastrointestinal morbidity unless the duodenum received excessive radiation doses. Reirradiation could also provide substantial IFFS, especially for patients with a GTV of <60.0 mL.

Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma.

PURPOSE: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). PATIENTS AND METHODS: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the ≥ grade 2 GD toxicity were investigated. RESULTS: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V25 for stomach and V35 for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for ≥ grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V25 ≤ 6.3 % and 57.1 % for V25 > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V35 ≤ 5.4 % and 45.9 % for V35 > 5.4 %. By multivariate analysis including the clinical factors, V25 for stomach and V35 for duodenum were the significant factors. CONCLUSION: EGD revealed that GD toxicity is common following RT for HCC. V25 for the stomach and V35 for the duodenum were the significant factors to predict ≥ grade 2 GD toxicity.

Demonstrating the benefits of corrective intraoperative feedback in improving the quality of duodenal hydrogel spacer placement.

PURPOSE: Pancreatic cancer is the fourth leading cause of cancer-related death with a 10% 5-year overall survival rate (OS). Radiation therapy (RT) in addition to dose escalation improves the outcome by significantly increasing the OS at 2 and 3 years but is hindered by the toxicity of the duodenum. Our group showed that the insertion of hydrogel spacer reduces duodenal toxicity, but the complex anatomy and the demanding procedure make the benefits highly uncertain. Here, we investigated the feasibility of augmenting the workflow with intraoperative feedback to reduce the adverse effects of the uncertainties. MATERIALS AND METHODS: We simulated three scenarios of the virtual spacer for four cadavers with two types of gross tumor volume (GTV) (small and large); first, the ideal injection; second, the nonideal injection that incorporates common spacer placement uncertainties; and third, the corrective injection that uses the simulation result from nonideal injection and is designed to compensate for the effect of uncertainties. We considered two common uncertainties: (1) "Narrowing" is defined as the injection of smaller spacer volume than planned. (2) "Missing part" is defined as failure to inject spacer in the ascending section of the duodenum. A total of 32 stereotactic body radiation therapy (SBRT) plans (33 Gy in 5 fractions) were designed, for four cadavers, two GTV sizes, and two types of uncertainties. The preinjection scenario for each case was compared with three scenarios of virtual spacer placement from the dosimetric and geometric points of view. RESULTS: We found that the overlapping PTV space with the duodenum is an informative quantity for determining the effective location of the spacer. The ideal spacer distribution reduced the duodenal V33Gy for small and large GTV to less than 0.3 and 0.1cc, from an average of 3.3cc, and 1.2cc for the preinjection scenario. However, spacer placement uncertainties reduced the efficacy of the spacer in sparing the duodenum (duodenal V33Gy: 1.3 and 0.4cc). The separation between duodenum and GTV decreased by an average of 5.3 and 4.6 mm. The corrective feedback can effectively bring back the expected benefits from the ideal location of the spacer (averaged V33Gy of 0.4 and 0.1cc). CONCLUSIONS: An informative feedback metric was introduced and used to mitigate the effect of spacer placement uncertainties and maximize the benefits of the EUS-guided procedure.

Planning design of locally advanced pancreatic carcinoma using 4DCT and IMRT/IGRT technologies.

BACKGROUND AND PURPOSE: to study the impact of the 4DCT imaging technique on radiotherapy planning for pancreatic carcinoma. To evaluate the possibility of IMRT/IGRT to increase the dose to PTV subvolume. MATERIAL AND METHODS: contrast-enhanced 4DCT scans of 15 patients (PTs) with unresectable pancreatic cancer were acquired. A 4DCT based PTV (4D-PTV) was created by the convolution of contours and then expanded for geometric uncertainties; a standard PTV (STD-PTV) was derived from a single CTV plus conventional margins. Two 3D conformal treatment (3DCRT) plans and one Helical Tomotherapy (HT) plan were generated with a prescription of 60 Gy. Regarding the 3DCRT plans, the 4D-PTV was considered as the target volume for one, and the STD-PTV for the other; the HT plans were performed only for 4D-PTV. Twelve of 15 PTs were admitted to a Phase I hypofractionated study (15 fractions). The prescribed dose was 44.25 Gy to the 4D-PTV and the PTV subvolume around vascular involvement was boosted from 50 to 55 Gy; before treatment, daily patient position was corrected using MVCT. RESULTS: 4D-PTVs were smaller than STD-PTVs with a volume reduction equal to 37%. 3DCRT plans on 4D-PTV showed a significant sparing of most OARs, the use of IMRT allowed a further significant dose reduction. In the Phase I study the PTV subvolume received up to 55 Gy with modest increase in dose to OARs. CONCLUSIONS: the 4DCT procedure decreases the overlap between PTV and OARs. HT technique, compared with 3DCRT, allows efficient dose sparing in particular for the duodenum. The IMRT/IGRT approach allows a safe dose escalation to PTV subvolume.

[Tripeptide restorates structure of duodenum at accelerated aging].

Effect of tripeptide on the process of postradiational restoration of duodenum in rats has been studied in model of accelerated aging. Geroprotective effect of tripeptide was connected with reparation of bloodstream in duodenum and increase proliferative activity of duodenal epiteliocytes.

Unrecognized digestive toxicities of radiation therapy.

The aim of this article is to review unrecognized toxicities resulting from radiation therapy of digestive neoplasms. Due to their precocious occurrence, acute toxicities are well-known by radiation oncologist, and their treatment well-established. Thus, acute toxicities will not be described in this review. We will focus on incidence, diagnosis, and management of late and uncommon toxicities occurring in the digestive tract and digestive organs. Prevention, by respecting healthy tissues constraints, is the main tool to reduce incidence of those rare complications. Nonetheless, once installed, late toxicities remain a major burden in terms of quality of life and can even be life threatening. Hence, information and education about their diagnosis and management is important.

Differential Recovery of Small Intestinal Segments after Partial-Body Irradiation in Non-Human Primates.

In the event of a radiological attack or accident, it is more likely that the absorbed radiation dose will be heterogeneous, rather than uniformly distributed throughout the body. This type of uneven dose distribution is known as partial-body irradiation (PBI). Partial exposure of the vital organs, specifically the highly radiosensitive intestines, may cause death, if the injury is significant and the post-exposure recovery is considerably compromised. Here we investigated the recovery rate and extent of recovery from PBI-induced intestinal damage in large animals. Rhesus macaques (Macaca mulatta) were randomly divided into four groups: sham-irradiated (0 Gy), 8 Gy PBI, 11 Gy PBI and 14 Gy PBI. A single dose of ionizing radiation was delivered in the abdominal region using a uniform bilateral anteroposterior and posteroanterior technique. Irradiated animals were scheduled for euthanasia on days 10, 28 or 60 postirradiation, and sham-irradiated animals on day 60. Intestinal structural injuries were assessed via crypt depth, villus height, and mucosal surface length in the four different intestinal regions (duodenum, proximal jejunum, distal jejunum and ileum) using H&E staining. Higher radiation doses corresponded with more injury at 10 days post-PBI and a faster recovery rate. However, at 60 days post-PBI, damage was still evident in all regions of the intestine. The proximal and distal ends (duodenum and ileum, respectively) sustained less damage and recovered more fully than the jejunum.

Oesophageal ulceration after selective internal radiation therapy in a patient with carcinoma of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) is defined as histologically confirmed metastases in the absence of an identifiable primary tumor. Patients with solely liver metastases from adenocarinomas represent the most frequent subgroup with an unfavourable prognosis. The medium survival averages 6 to 9 months. No chemotherapheutic standard has been established. CASE: We present a patient with hepatic CUP. After cycles of chemotherapy and hemihepatectomy the tumor returned and showed hepatic progression. The patient was evaluated for selective internal radiation therapy (SIRT). Three years after diagnosis she is still alive and tumorfree. Despite a good result and disease control our patient suffered radiation-induced ulceration in the oesophagus, stomach, and duodenum. This side effect appears in up to 12 % of patients, often very late after treatment, is refractory to pharmacotherapy and persistent over a long time. CONCLUSIONS: SIRT is a new, effective treatment in patients with hepatic CUP. Because of the anticipated increase of this therapy, adverse side effects such as ulcerations in the upper-GI tract secondary to ectopic implantation of microspheres may be seen more commonly. Awareness of this and the recognition of microspheres in biopsies is cardinal for appropriate management and maintenance of the patient's quality of life.

A Retrospective Study of the Dosimetric Parameters and Duodenal Toxicity in Patients With Upper Gastrointestinal and Gynaecological Cancers Treated With Radiation Therapy.

AIMS: The duodenum is a critical organ at risk while planning radiation for gastrointestinal cancers or para-aortic nodes from gynaecological cancers due to the close proximity to the target volumes. The aim of this study was to assess the dosimetric parameters of the duodenum received during radiotherapy to upper gastrointestinal and gynaecological malignancies and their correlation with clinical toxicity. MATERIALS AND METHODS: All adult patients who were treated with radiotherapy for primary upper gastrointestinal cancers (liver, stomach, pancreas, gall bladder) and patients with gynaecological cancers who were treated with extended fields in view of para-aortic nodal involvement from 1 January 2010 to 31 July 2015 were considered for the study. The radiation dose prescription was 45 Gy to the elective clinical target volume and 52.5-60 Gy to the gross nodal volume. The planning computed tomography scan was retrieved and the dose-volume histogram parameters for the duodenum were extracted. The relative volumes of duodenum receiving a dose from 40 to 55 Gy in increments of 5 Gy (V40Gy, V45Gy, V50Gy, V55Gy) were also noted. RESULTS: Of the 258 patients assessed, 30 patients (12.1%) were detected to have grade 2-4 toxicities related to the duodenum as detected on endoscopy. Most had grade 3 toxicity - 18 patients were diagnosed with grade 3 toxicity and four patients had grade 4 toxicity. The most common toxicity noted was duodenal ulceration seen in 16 patients. The other toxicities were duodenal stricture in eight patients, duodenal perforation in five patients and one patient was reported to have duodenal fistula. The patients with duodenum receiving V55Gy ≥ 1 cm3 (7.7% versus 3.8%, P = 0.014) and V50Gy ≥ 4 cm3 (7.7% versus 3.8%, P = 0.014) had higher grade ≥2 duodenal toxicity. CONCLUSION: A threshold level of V55Gy ≥ 1 cm3 and V50Gy ≥ 4 cm3 for the duodenum is predictive of clinically significant grade 2 and higher toxicity and could serve as valid dose constraints for the duodenum.

Mitigation of Radiation-induced Gastrointestinal System Injury using Resveratrol or Alpha-lipoic Acid: A Pilot Histopathological Study.

AIM: In this study, we aimed to determine possible mitigation of radiationinduced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid. BACKGROUND: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole-body exposure to radiation. Its side effects reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol. OBJECTIVE: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. METHODS: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole-body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma-ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon. RESULTS AND DISCUSSION: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury. CONCLUSION: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

Epitaxially Strained CeO2 /Mn3 O4 Nanocrystals as an Enhanced Antioxidant for Radioprotection.

Nanomaterials with antioxidant properties are promising for treating reactive oxygen species (ROS)-related diseases. However, maintaining efficacy at low doses to minimize toxicity is a critical for clinical applications. Tuning the surface strain of metallic nanoparticles can enhance catalytic reactivity, which has rarely been demonstrated in metal oxide nanomaterials. Here, it is shown that inducing surface strains of CeO2 /Mn3 O4 nanocrystals produces highly catalytic antioxidants that can protect tissue-resident stem cells from irradiation-induced ROS damage. Manganese ions deposited on the surface of cerium oxide (CeO2 ) nanocrystals form strained layers of manganese oxide (Mn3 O4 ) islands, increasing the number of oxygen vacancies. CeO2 /Mn3 O4 nanocrystals show better catalytic activity than CeO2 or Mn3 O4 alone and can protect the regenerative capabilities of intestinal stem cells in an organoid model after a lethal dose of irradiation. A small amount of the nanocrystals prevents acute radiation syndrome and increases the survival rate of mice treated with a lethal dose of total body irradiation.

[Dosimetric impact of breath-hold in the treatment of hepatocellular carcinoma by conformal radiation therapy]. / Impact dosimétrique du blocage respiratoire dans le traitement du carcinome hépatocellulaire par irradiation de conformation.

OBJECTIVE: To evaluate the dosimetric impact of breath-hold during radiotherapy of hepatocellular carcinoma (HCC) and to determinate the optimal respiratory phase for treatment (exhale or inhale). PATIENTS AND METHODS: Two CT scans were performed in inhale and in exhale in 20 patients with HCC. The GTV was delineated slice by slice on the inspiration breath hold acquisition (GTV(insp)) and on the expiration breath hold acquisition (GTV(exp)). The superposition of two GTV allowed to obtain the global GTV (free respiration). PTV was defined by adding a margin of 1cm around each GTV. The liver, the duodenum, the two kidneys, the stomach and the spinal cord were delineated on each acquisition as organs at risk (OAR). Three dosimetric plans were created on inspiration, expiration and on global PTV. RESULTS: The mean reduction in the volume of PTV with conformal radiation therapy (3D-CRT) in the hold-breath group compared to the free respiration group was of 33.5+/-11.9%. The average difference of V50%, V20, V30, V40 and V50 were around 4% in favor of the breath hold. The average value of NTCP was 8.9% in free respiration, 4.5% in expiration and 3.2% in inspiration. Further improvement in the OARs dosimetric parameters for the breath hold was observed. CONCLUSION: Compared to the conformal radiotherapy with free respiration, the breath-hold allows reducing the volume of the PTV and the doses to the healthy liver and organs at risk. The use of this modality during different radiotherapy techniques (3D-CRT, IMRT and stereotactic) may be recommended. No difference in dosimetric value has been observed between the breath hold in expiratory and inspiratory phases.

Reduction of dose to duodenum with a refined delineation method of Para-aortic region in patients with locally advanced cervical Cancer receiving prophylactic extended-field radiotherapy.

BACKGROUND: To compare irradiation dose to the second and third portions of duodenum (Duo2 and Duo3) with a new refined and old delineation method of para-aortic region for patients with locally advanced cervical cancer (LACC) receiving prophylactic extended-field radiotherapy (EFRT). METHODS: Twenty consecutive patients with LACC were treated with prophylactic EFRT from January 2016 to January 2017 at our institute. Two delineation methods of para-aortic region were designed for each patient, the old delineation method ensured a full coverage of aortic and inferior vena cava, while the right paracaval region above L3 was omitted from CTV in the new delineation method. Patients received a dose of 50.4Gy in 28 fractions for PCTV and a dose of 60.2Gy in 28 fractions for PGTV with volumetric-modulated arc therapy (VMRT). The dose delivered to Duo2 and Duo3 with these two delineation methods were compared. RESULTS: All treatment plans achieved excellent target volume coverage with 95% of PCTV receiving 50.4Gy and 95% of PGTV receiving 60.2Gy. There was no difference between delineation methods in low dose level (V5, V10, V15, V20, V25) for Duo2 and Duo3. The V30, V35, V40, V45, V50, Dmax, Dmean and D2cc for Duo2 with the new and old delineation methods were 55.76% vs 80.54% (P = 0.009), 34.72% vs 70.91% (P < 0.001), 18.69% vs 55.46% (P < 0.001), 8.20% vs 41.49% (P < 0.001), 1.86% vs 21.60% (P < 0.001), 49.58Gy vs 52.91Gy (P = 0.002), 30.38Gy vs 39.22Gy (P = 0.001) and 37.90Gy vs 48.64Gy (P < 0.001) respectively. For Duo3, the new delineation method achieved significant advantages in V30, V35, V40, V45, V50 and Dmean over the old one (96.82% vs 99.25%, P = 0.021; 89.65% vs 97.21%, P = 0.001; 79.50% vs 93.18%, P < 0.001; 65.63% vs 82.93%, P < 0.001; 43.39% vs 65.60%, P < 0.001; 46.09Gy vs 49.24Gy, P < 0.001), no deference was observed regarding D2cc and Dmax with these two delineation methods. CONCLUSION: With the new delineation method of para-aortic area in prophylactic EFRT, significant reduction of irradiation dose to the second and third portions of duodenum in high dose area was obtained. This may further lower the incidence of duodenal toxicity when performing prophylactic EFRT for patients with LACC.

Fasting Reduces Intestinal Radiotoxicity, Enabling Dose-Escalated Radiation Therapy for Pancreatic Cancer.

PURPOSE: Chemotherapy combined with radiation therapy is the most commonly used approach for treating locally advanced pancreatic cancer. The use of curative doses of radiation in this disease setting is constrained because of the close proximity of the head of the pancreas to the duodenum. The purpose of this study was to determine whether fasting protects the duodenum from high-dose radiation, thereby enabling dose escalation for efficient killing of pancreatic tumor cells. METHODS AND MATERIALS: C57BL/6J mice were either fed or fasted for 24 hours and then exposed to total abdominal radiation at 11.5 Gy. Food intake, body weight, overall health, and survival were monitored. Small intestines were harvested at various time points after radiation, and villi length, crypt depth, and number of crypts per millimeter of intestine were determined. Immunohistochemistry was performed to assess apoptosis and double-strand DNA breaks, and microcolony assays were performed to determine intestinal stem cell regeneration capacity. A syngeneic KPC model of pancreatic cancer was used to determine the effects of fasting on the radiation responses of both pancreatic cancer and host intestinal tissues. RESULTS: We demonstrated that a 24-hour fast in mice improved intestinal stem cell regeneration, as revealed by microcolony assay, and improved host survival of lethal doses of total abdominal irradiation compared with fed controls. Fasting also improved survival of mice with orthotopic pancreatic tumors subjected to lethal abdominal radiation compared with controls with free access to food. Furthermore, fasting did not affect tumor cell killing by radiation therapy and enhanced γ-H2AX staining after radiation therapy, suggesting an additional mild radiosensitizing effect. CONCLUSIONS: These results establish proof of concept for fasting as a dose-escalation strategy, enabling ablative radiation in the treatment of unresectable pancreatic cancer.

Hypofractionated intensity-modulated radiotherapy in locally advanced unresectable pancreatic cancer: A pilot study.

PURPOSE: To test feasibility and safety of hypofractionated intensity modulated radiotherapy (H-IMRT) in pancreatic adenocarcinoma (PAC) treatment. METHODS: Patients with unresectable nonmetastatic PAC were prospectively enrolled on a pilot study. Patients received H-IMRT to gross tumor volume to a total dose of 52 Gy (4 Gy/fraction). Toxicity rates, duodenal dosimetric parameters, and clinical outcomes were evaluated. RESULTS: Ten patients received H-IMRT regimen. Objective tumor response was recorded in all patients but one. Gastrointestinal toxicity was the most common acute side effect and its severity moderately correlated with duodenal maximum dose (ρ = 0.46) and percentage of duodenal volume exposed to 5 Gy (ρ = 0.46). The 1-year overall and disease-free survival were 83.3% and 68.6%, respectively. CONCLUSION: H-IMRT seems to guarantee a high local control rate without severe toxicity. Its use in unresectable nonmetastatic PAC needs to be further investigated.

[Extrapineal melatonin in processes of accelerated and premature aging in rats].

In order to reveal the participation of extrapineal melatonin in ageing processes, Wistar rats were (a) exposed to small doses of gamma irradiation and (b) subjected to pinealectomy. It was showed that during a radiation-induced aging simulation occurs a manifest hypoplasia of MT-responder cells in the mucosa of the duodenum, and the number of mast cells is reduced by ten times. During pinealectomy the number of MT-positive enterochromaffin cells increases.

Dose Prediction Model for Duodenum Sparing With a Biodegradable Hydrogel Spacer for Pancreatic Cancer Radiation Therapy.

PURPOSE: We previously have shown the feasibility of duodenum sparing using a biodegradable hydrogel spacer in pancreatic cancer radiation therapy. In this study, we propose an overlap volume histogram (OVH) prediction model to select patients who might benefit from hydrogel placement and to predict the hydrogel spacing required to achieve clinical constraints. METHODS AND MATERIALS: OVH metrics for the duodenum were collected from the stereotactic body radiation therapy plans of 232 patients with unresectable pancreatic cancer (33 Gy in 5 fractions). OVH metrics L9cc and L3cc were defined as the tumor volume expansion distance at which 9 cm3 and 3 cm3 volumes of the duodenum overlap with tumor. D9cc and D3cc of the duodenum were defined as the dose-volume histogram dose to 9 cm3 and 3 cm3, respectively, of the duodenum. Prediction models were established by linear regression between Lx and Dx, where x = 3 cm3 and 9 cm3. OVH thresholds were obtained for predicting the target spacer thickness. The accuracy of the prediction model was then evaluated using treatment plans on pre-and post-hydrogel injection computed tomography scans from 2 cadaver specimens and 6 patients with previously treated locally advanced pancreatic cancer with simulated spacer. RESULTS: Linear regression analysis showed a significant correlation between Lx and Dx (r2 = 0.51 and 0.51 for L3cc-D3cc and L9cc-D9cc, respectively; both P < .01). The OVH thresholds were Lˆ3cc = 7 mm and Lˆ9cc = 13 mm. The observed planning doses D3cc and D9cc of duodenum from pre-and post-hydrogel injection computed tomography scans of cadaver specimens and clinical patients with simulated spacer using predicted target spacer thickness were within the OVH model prediction range. CONCLUSION: Our model may predict which patients require placement of a hydrogel spacer before stereotactic body radiation therapy to meet predefined dose constraints. Furthermore, by predicting the required target hydrogel thickness, the spacer injection can be better guided to improve efficacy.

A four-dimensional CT-based evaluation of techniques for gastric irradiation.

PURPOSE: To evaluate three-dimensional conformal (3D-CRT), intensity-modulated (IMRT) and respiration-gated radiotherapy (RGRT) techniques for gastric irradiation for target coverage and minimization of renal doses. All techniques were four-dimensional (4D)-CT based, incorporating the intrafractional mobility of the target volume and organs at risk (OAR). METHODS AND MATERIALS: The stomach, duodenal C-loop, and OAR (kidneys, liver, and heart) were contoured in all 10 phases of planning 4D-CT scans for five patients who underwent abdominal radiotherapy. Planning target volumes (PTVs) encompassing all positions of the stomach (PTV(all phases)) were generated. Three respiratory phases for RGRT in inspiration and expiration were identified, and corresponding PTV(inspiration) and PTV(expiration) and OAR volumes were created. Landmark-based fields recommended for the Radiation Therapy Oncology Group (RTOG) 99-04 study protocol were simulated to assess PTV coverage. IMRT and 3D-CRT planning with and without additional RGRT planning were performed for all PTVs, and corresponding dose volume histograms were analyzed. RESULTS: Use of landmark-based fields did not result in full geometric coverage of the PTV(all phases) in any patient. IMRT significantly reduced mean renal doses compared with 3D-CRT (15.0 Gy +/- 0.9 Gy vs. 20.1 Gy +/- 9.3 Gy and 16.6 Gy +/- 1.5 Gy vs. 32.6 Gy +/- 7.1 Gy for the left and right kidneys, respectively; p = 0.04). No significant increase in renal sparing was seen when adding RGRT to either 3D-CRT or IMRT. Tolerance doses to the other OAR were not exceeded. CONCLUSIONS: Individualized field margins are essential for gastric irradiation. IMRT plans significantly reduce renal doses, but the benefits of RGRT in gastric irradiation appear to be limited.

Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data.

BACKGROUND AND PURPOSE: Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data. MATERIAL AND METHODS: A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials. RESULTS: Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n=0.070, m=0.46, TD50(1) [Gy]=183.8, while the values for the model incorporating the individual patient data were n=0.193, m=0.51, TD50(1) [Gy]=299.1. CONCLUSIONS: LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose.