Bone Marrow Sparing Research Articles

Dosimetric analysis and acute toxicity comparison of bone marrow sparing intensity-modulated radiation therapy versus three-dimensional conformal therapy with concurrent chemotherapy for the treatment of cervical carcinoma: A prospective single institutional study

Background: The aim of the study was to compare the dosimetry and acute toxicities of bone marrow sparing intensity-modulated radiation therapy (BMS-IMRT) and three-dimensional conformal radiation techniques (3DCRT) in locally advanced cervical cancer. Materials and Methods: This is a hospital-based prospective randomized study and histologically proven locally advanced cervical carcinoma patients were selected for the analysis. A total of thirty patients were equally allocated in the two treatment arms: BMS-IMRT and 3DCRT. External beam radiation therapy was delivered to a dose of 50 Gy/25# followed by high dose rate brachytherapy along with concurrent chemotherapy. The target volumes and the organs at risks were delineated. The BM comprised pelvic BM (PBM); lumbosacral BM (LSBM); ilium BM (IBM) and Ischium, Pubis and Pelvic femora together constituting lower PBM (LPBM). Results: BMS-IMRT was superior to the 3DCRT arm in reducing the dose to the PBM, small bowel, rectum, and bladder. On comparison of the BM dose volume histogram, the P value was significant (BMS IMRT vs. 3DCRT) in the higher dose range (30 and 40 Gy) for the IBM, LPBM, and whole pelvis BM. However, the difference in the low-dose irradiation (10 and 20 Gy) region was not significant. Furthermore, in the LSBM region, BMS IMRT was superior at all dose levels with no significant P value. Acute toxicities were higher in the 3DCRT arm. Conclusion: Thus, BMS-IMRT resulted in significant reduction of dose to the PBM. This can help in reducing the hematologic toxicities associated with pelvic radiation.

Which Bone Marrow Sparing Strategy and Radiotherapy Technology Is Most Beneficial in Bone Marrow-Sparing Intensity Modulated Radiation Therapy for Patients With Cervical Cancer?

BackgroundTo evaluate the dosimetric parameters of different bone marrow sparing strategies and radiotherapy technologies and determine the optimal strategy to reduce hematologic toxicity associated with concurrent chemoradiation (cCRT) for cervical cancer.MethodsA total of 15 patients with Federation International of Gynecology and Obsterics (FIGO) Stage IIB cervical cancer treated with cCRT were re-planned for bone marrow (BM)-sparing plans. First, we determined the optimal BM sparing strategy for intensity modulated radiotherapy (IMRT), including a BMS-IMRT plan that used total BM sparing (IMRT-BM) as the dose-volume constraint, and another plan used os coxae (OC) and lumbosacral spine (LS) sparing (IMRT-LS+OC) to compare the plan without BM-sparing (IMRT-N). Then, we determined the optimal technology for the BMS-IMRT, including fixed-field IMRT (FF-IMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). The conformity and homogeneity of PTV, exposure volume of OARs, and efficiency of radiation delivery were analyzed.ResultsCompared with the IMRT-N group, the average volume of BM that received ≥10, ≥20, ≥30, and ≥40 Gy decreased significantly in both two BM-sparing groups, especially in the IMRT-LS+OC group, meanwhile, two BMS-IMRT plans exhibited the similar effect on PTV coverage and other organs at risk (OARs) sparing. Among three common IMRT techniques in clinic, HT was significantly less effective than VMAT and FF-IMRT in the aspect of BM-Sparing. Additionally, VMAT exhibited more efficient radiation delivery.ConclusionWe recommend the use of VMAT with OC and LS as separate dose-volume constraints in cervical cancer patients aiming at reducing hematologic toxicity associated with cCRT, especially in developing countries.

Comparison of IMRT plans with and without bone marrow sparing for the treatment of cervical cancer

Background: The aim of the present study was to compare intensity-modulated radiation therapy (IMRT) plan with Bone Marrow sparing (BM-IMRT) and plan without Bone Marrow Sparing (N-IMRT). Materials and Methods: Fifteen cases of cervical cancer cases were selected for retrospective analysis. All the cases were previously treated with normal IMRT. For this study, plans with BM-IMRT were created again for all patients following Radiation Therapy Oncology Group (RTOG) guidelines. The prescribed dose (PD) of 50Gy in 25 fractions was given. The plan having coverage of 95% of PTV receiving 95% of prescribed dose was accepted. The plans were compared on the basis of planning target volume (PTV) coverage (dose to 2%, 98% of target), Constraints of OAR (Organs at Risk) were volume of 40% < 40Gy for normal bladder and rectum, (volume receiving dose 5Gy) V5

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

Simple SummaryHematological toxicity may be a consistent issue in anal cancer patients undergoing concurrent chemo-radiation, with a potentially detrimental effect on clinical outcomes and patient compliance to treatment. Chemotherapy is the most important trigger, since it induces myelosuppression, but radiation dose delivered to the hematopoietically active bone marrow (BM) also plays an important role. Active bone marrow can be identified using functional imaging with 18-Fluoro-2-deoxy-glucose positron emission tomography (18FDG-PET) and selectively spared during radiation delivery via intensity-modulated radiotherapy (IMRT). We investigated, within a prospective phase II trial, the potential effectiveness of targeted avoidance of active BM comprised within pelvic bones in reducing the acute hematologic toxicity profile of anal cancer patients undergoing concomitant chemo-radiation for squamous cell carcinoma of the anus. The results of the first step of the study fulfilled the criteria to define BM-sparing IMRT as “promising” and to continue with the second step of the phase II trial.Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon’s design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

Acute Radiation-induced Lung Injury in the Non-human Primate: A Review and Comparison of Mortality and Co-morbidities Using Models of Partial-body Irradiation with Marginal Bone Marrow Sparing and Whole Thorax Lung Irradiation

The nonhuman primate, rhesus macaque, is a relevant animal model that has been used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality of radiation-induced lung injury. Herein, a literature review of published studies showing the evolution of lethal lung injury characteristic of the delayed effects of acute radiation exposure between the two significantly different exposure protocols, whole thorax lung irradiation and partial-body irradiation with bone marrow sparing in the nonhuman primate, is provided. The selection of published data was made from the open literature. The primary studies conducted at two research sites benefitted from the similarity of major variables; namely, both sites used rhesus macaques of approximate age and body weight and radiation exposure by LINAC-derived 6 MV photons at dose rates of 0.80 Gy min and 1.00 Gy min delivered to the midline tissue via bilateral, anterior/posterior, posterior/anterior geometry. An advantage relative to sex difference resulted from the use of male and female macaques by the Maryland and the Washington sites, respectively. Subject-based medical management was used for all macaques. The primary studies (6) provided adequate data to establish dose response relationships within 180 d for the radiation-induced lung injury consequent to whole thorax lung irradiation (male vs. female) and partial-body irradiation with bone marrow sparing exposure protocols (male). The dose response relationships established by probit analyses vs. linear dose relationships were characterized by two main parameters or dependent variables, a slope and LD50/180. Respective LD50/180 values for the primary studies that used whole thorax lung irradiation for respective male and female nonhuman primates were 10.24 Gy [9.87, 10.52] (n = 76, male) and 10.28 Gy [9.68, 10.92] (n = 40, female) at two different research sites. The respective slopes were steep at 1.73 [0.841, 2.604] and 1.15 [0.65, 1.65] probits per linear dose. The LD50/180 value and slope derived from the dose response relationships for the partial-body irradiation with bone marrow sparing exposure was 9.94 Gy [9.35, 10.29] (n = 87) and 1.21 [0.70, 1.73] probits per linear dose. A secondary study (1) provided data on limited control cohort of nonhuman primates exposed to whole thorax lung irradiation. The data supported the incidence of clinical, radiographic, and histological indices of the dose-dependent lung injury in the nonhuman primates. Tertiary studies (6) provided data derived from collaboration with the noted primary and secondary studies on control cohorts of nonhuman primates exposed to whole thorax lung irradiation and partial-body irradiation with bone marrow sparing exposure. These studies provided a summary of histological evidence of fibrosis, inflammation and reactive/proliferative changes in pneumonocytes characteristic of lung injury and data on biomarkers for radiation-induced lung injury based on matrix-assisted laser desorption ionization-mass spectrometry imaging and gene expression approaches. The available database in young rhesus macaques exposed to whole thorax lung irradiation or partial-body irradiation with bone marrow sparing using 6 MV LINAC-derived radiation with medical management showed that the dose response relationships were equivalent relative to the primary endpoint all-cause mortality. Additionally, the latency, incidence, severity, and progression of the clinical, radiographic, and histological indices of lung injury were comparable. However, the differences between the exposure protocols are remarkable relative to the demonstrated time course between the multiple organ injury of the acute radiation syndrome and that of the delayed effects of acute radiation exposure, respectively.

PH-0486: Dosimetric comparison of bone marrow sparing VMAT VS 3DCRT in locally advanced rectal cancer

PH-0486: Dosimetric comparison of bone marrow sparing VMAT VS 3DCRT in locally advanced rectal cancer

PD-0536: Bone-marrow sparing IMRT for anal cancer patients: a prospective phase II trial

PD-0536: Bone-marrow sparing IMRT for anal cancer patients: a prospective phase II trial

Assessment of Impact of Bone Marrow Sparing for Hematological and Gastrointestinal Toxicities in Cervical Cancer with External Beam Radiation Therapy

Assessment of Impact of Bone Marrow Sparing for Hematological and Gastrointestinal Toxicities in Cervical Cancer with External Beam Radiation Therapy

Proteomics of Non-human Primate Plasma after Partial-body Radiation with Minimal Bone Marrow Sparing.

High-dose radiation exposure results in organ-specific sequelae that occurs in a time- and dose-dependent manner. The partial body irradiation with minimal bone marrow sparing model was developed to mimic intentional or accidental radiation exposures in humans where bone marrow sparing is likely and permits the concurrent analysis of coincident short- and long-term damage to organ systems. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the plasma proteome of non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing with 6 MV LINAC-derived photons at 0.80 Gy min over a time period of 3 wk. The plasma proteome was analyzed by liquid chromatography-tandem mass spectrometry. A number of trends were identified in the proteomic data including pronounced protein changes as well as protein changes that were consistently upregulated or downregulated at all time points and dose levels interrogated. Pathway and gene ontology analysis were performed; bioinformatic analysis revealed significant pathway and biological process perturbations post high-dose irradiation and shed light on underlying mechanisms of radiation damage. Additionally, proteins were identified that had the greatest potential to serve as biomarkers for radiation exposure.

Approach to radiation therapy in the Jehovah's Witness patient: An overview.

Jehovah's Witnesses are well-known in the medical community for their inability to accept blood products. Novel methods of treatment are often needed to avoid anemia and hematologic toxicity as inability to receive blood products may increase the risk of treatment related complications. We provide an overview of radiation treatment for Jehovah's Witness patients with an emphasis on bone marrow sparing strategies with intensity modulated radiation therapy (IMRT) to minimize hematologic toxicity.

Abstract 6249: CBX-12: A low pH targeting alphalex™-exatecan conjugate for the treatment of solid tumors

Abstract Topoisomerase inhibitors are potent DNA damaging agents with great potential as anti-cancer drugs for a wide range of solid tumors. However, dose-limiting toxicities such as myelosuppression and gastric toxicity have prevented them from reaching their full clinical potential. Targeting topoisomerase inhibitors with antibodies (i.e. antibody-drug conjugates; ADCs) may enhance the therapeutic window of these agents, but this approach typically limits applicability to a small subset of patients with tumors expressing the target antigen. We recently developed the alphalexTM tumor-targeting platform to overcome the limitations of ADC-based therapeutic strategies. Rather than targeting a specific antigen, alphalexTM consists of a unique variant of pH-Low Insertion Peptide, (pHLIP®; references 1-3) which targets the low pH environment of the tumor, a universal feature characteristic of all tumors due to the Warburg effect. These alphalexTM conjugates form an alpha helix only in low pH conditions, allowing for insertion of the peptide within the cancer cell membrane, delivery of C-terminal warheads across the membrane, and subsequent intracellular release of the agent via glutathione reduction of the linker, thereby allowing for tumor-specific intracellular delivery in an antigen-independent manner. We report the discovery and development of CBX-12, an alphalexTM conjugate of the potent topoisomerase inhibitor, exatecan. CBX-12 provides additional proof of mechanism to the alphalexTM platform by displaying remarkable tumor-targeting properties in preclinical models. CBX-12 displays enhanced stability in plasma in vivo, undergoing only 0.003% warhead release over 30 hours in circulation and demonstrating exquisite selectivity for tumor over normal tissues in mouse tumor models. Notably, CBX-12 allows for efficient delivery of exatecan into tumors due to a highly optimized cleavable linker, allowing CBX-12 to display extraordinary efficacy in a HER2-negative tumor model in an antigen-independent manner. At 10 mg/kg, CBX-12 treatment almost completely suppressed growth of human colorectal tumors in mice, with complete sparing of bone marrow. In contrast, in animals dosed with the equimolar free exatecan (1.15 mg/kg) there was substantial tumor growth accompanied by neutropenia and weight loss. This superior profile of CBX-12 allow us to greatly enhance efficacy relative to dosing equimolar amounts of unconjugated exatecan, which causes significant, dose-limiting bone marrow toxicity. We have demonstrated that CBX-12 is both safe and has potent anti-tumor activity in preclinical models, and we plan to rapidly move forward with the clinical development of CBX-12 as our lead candidate.

Pelvic bone marrow sparing intensity modulated radiotherapy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial

PurposeTo test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing grade 2 or higher hematological toxicity (HT2+) for patients with cervical cancer treated with concurrent chemoradiotherapy.Methods and materialsA total of 164 patients with Stage Ib2–IIIb cervical cancer were prospectively enrolled from March 2018 to March 2019 at a single center and were randomly allocated into the PBMS group or the control group. The control group received weekly cisplatin concurrently with IMRT, followed by intracavitary brachytherapy. The PBMS group additionally received PBM dose constraint. The dosimetric parameters of the pelvic bone (PB) and the subsites including hip bone (HIP) and lumbosacral spine (LSS) and the corresponding bone marrow were recorded. The endpoint of the trial was acute hematologic or gastrointestinal toxicity. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints.ResultsEighty-two patients in the PBMS group and 82 in the control group were enrolled for statistical analysis. The incidence of HT2+ in the PBMS group was 50.0%, significantly lower than the 69.5% incidence in the control group (P = 0.02). Patients with PB V40 ≥ 28% were more likely to experience HT2+ (OR = 2.85, P = 0.006), while the incidence of grade 2 or higher gastrointestinal toxicity (GT2+) events did not differ significantly between the two groups (P > 0.05). Dosimetric parameters of LSS showed stronger associations with HT2+ than other subsites. The patients with LSS V10 ≥ 87% and LSS mean ≥ 39 Gy were more likely to experience HT2+ (OR = 3.13, P = 0.001;OR = 3.03, P = 0.002, respectively).ConclusionPBMS-IMRT reduced HT compared with IMRT alone. Efforts to maintain LSS V10 < 87%, LSS mean < 39 Gy and PB V40 < 28% simultaneously may reduce the risk of HT2 +.Trial registrationThe trial was registered with Chinese clinical trial registry (ChiCTR1800015069).

A Multi-atlas Approach for Active Bone Marrow Sparing Radiation Therapy: Implementation in the NRG-GY006 Trial

Sparing active bone marrow (ABM) can reduce acute hematologic toxicity in patients undergoing chemoradiotherapy for cervical cancer, but ABM segmentation based on positron emission tomography/computed tomography (PET/CT) is costly. We sought to develop an atlas-based ABM segmentation method for implementation in a prospective clinical trial. A multiatlas was built on a training set of 144 patients and validated in 32 patients from the NRG-GY006 clinical trial. ABM for individual patients was defined as the subvolume of pelvic bone greater than the individual mean standardized uptake value on registered 18F-fluorodeoxyglucose PET/CT images. Atlas-based and custom ABM segmentations were compared using the Dice similarity coefficient and mean distance to agreement and used to generate ABM-sparing intensity modulated radiation therapy plans. Dose-volume metrics and normal tissue complication probabilities of the two approaches were compared using linear regression. Atlas-based ABM volumes (mean [standard deviation], 548.4 [88.3] cm3) were slightly larger than custom ABM volumes (535.1 [93.2] cm3), with a Dice similarity coefficient of 0.73. Total pelvic bone marrow V20 and Dmean were systematically higher and custom ABM V10 was systematically lower with custom-based plans (slope: 1.021 [95% confidence interval (CI), 1.005-1.037], 1.014 [95% CI, 1.006-1.022], and 0.98 [95% CI, 0.97-0.99], respectively). We found no significant differences between atlas-based and custom-based plans in bowel, rectum, bladder, femoral heads, or target dose-volume metrics. Atlas-based ABM segmentation can reduce pelvic bone marrow dose while achieving comparable targetandother normal tissue dosimetry. This approach may allow ABM sparing in settings where PET/CT is unavailable.

Retrospective Dosimetric analysis of Bone marrow sparing vs non bone marrow sparing Image Guided Volumetric Modulated Arc Therapy in intact Carcinoma Cervix patients

ABSTRACT Aim: Aim of this study was to compare dosimetric parameters of bone marrow (BM) and non bone marrow sparing with state of the art technique image guided volumetric modulated arc therapy in the treatment of Carcinoma Cervix. Methods and Materials: The retrospective Dosimetric study was conducted on 10 consecutive patients of biopsy-proven invasive cervical cancer attending the outpatient department of Geetanjali cancer centre. For treatment planning, patients were scanned on a GE Optima-520, 16 slice fan-beam CT (FBCT) scanner with 2.5 mm slice thickness in the supine position on a customized vacuum cushion with simulation tattoos and alignment lasers. All the simulation scans were taken after following a bladder and bowel preparation protocol, aimed at an empty rectum and full bladder, starting prior to the initial planning scan and continuing throughout the treatment. The prescribed dose to PTV was 50Gy in 25 fractions (2Gy/fraction) and from second week of radiotherapy 50mg/m2/week cisplatin chemotherapy was administered for five weeks. Two sets of plans were generated for all the 10 patients using Volumetric Arc Radiotherapy (VMAT) in Monaco v 5.11.02(Elekta, Crawley, UK) treatment planning system. Keeping all constraints in mind planning optimization was performed with no compromise in coverage of PTV. Results: In the present study V5, V10, V20, V30 were all significantly lower in BMS-IG/VMAT plan . Maximum significance was noted at V20. Value of V40 is lower in BM-IG/VMAT plan, but statistically not significant. Conclusion: Treatment of carcinoma cervix is restricted as a result of toxicity of the surrounding normal structures and HT. HT could be significantly reduced by bone marrow sparing, which could be aided by IGRT/VMAT. This modality could allow completion of treatment with prescribed dose and concurrent chemotherapy in allotted stipulated time. More prospective randomized control trials are needed, to prove its efficacy. key words: bone marrow sparing, hematological toxicity, Image Guidance/Volumetric Modulated Arc Therapy

Effect of Pelvic Bone Marrow-Sparing on Acute Hematologic Toxicity in Rectal Cancer Patients Undergoing Chemoradiotherapy

To investigate whether pelvic bone marrow sparing (PBMS) could reduce the incidence of acute hematologic toxicity in rectal cancer patients undergoing chemo-radiotherapy. 84 rectal cancer patients were selected and divided into the IMRT Group (42 cases) and the PBMS-IMRT Group (42 cases). All patients underwent concurrent chemo-radiotherapy. The PTV was prescribed with a total dose of 50∼50.4Gy in 1.8∼2Gy fractions. Capecitabine combined was administered concurrently with pelvic radiation. The pelvic bone was contoured both for the PBMS-IMRT and IMRT groups. Only the pelvic bone in PBMS-IMRT group was prescribed by:V10≤85%,V20≤65%,V30≤45%.The mean dose (Dmean) and the volume of each organ at risk (OAR) with dose range from 5 to 50Gy (e.g., V 5, V10, V15, V20, V25, V30, V35, V40, V45, andV50) was calculated for all the patients from the two groups. The patient acute hematologic toxicity (e.g. patient with symptoms of leukopenia, neutropenia, anemia, or thrombocytopenia) was recorded according to RTOG scoring scale. Independent sample t test were applied for the dose-volume parameters, and card square analysis for clinical parameters. In terms of the OAR dose-volume parameters, the V5∼V35 and Dmean for the pelvic bone, left femoral head and the right femoral head significantly (p<0.05) decreased for the PBMS-IMRT Group compared with the IMRT group. There was no significant difference in any dose-volume parameters for the bladder. As for PTV dose distribution, there was a significant (p=0.001) improvement of the target conformity in the PBMS-IMRT group. In addition, the dose homogeneity was also improved by 14.5% for this group, although not significantly (P=0.108). For the following acute hematologic toxicity observation, the numbers of the patients with grade 0, 1, 2, 3, 4 were 12, 6, 14, 10, and 0 respectively for the IMRT group. Meanwhile the corresponding numbers were 10, 19, 12, 1, and 0 for PBMS-IMRT group. The incidence of grade 2 or upper acute hematologic toxicity in the PBMS-IMRT group was significantly reduced (31%, 13/42 vs. 57.1%, 24/42, p=0.027). There was no incidence of grade 2 or upper acute cystitis in both of the two groups. The marrow-sparing of the pelvic bone significantly reduces its dosage as well as the left and right femoral head. Patients with pelvic bone marrow-sparing had lower incidence of the grade 2 or upper acute hematologic toxicity compared with those without marrow-paring. Pelvic bone marrow-sparing can benefit patients with rectal cancer undergoing chemo-radiotherapy.

Adjuvant Bone-Marrow Sparing IMRT in Endometrial Cancer Patients Treated with Sequential Chemotherapy- Does it Help with Completion Rate?

Postoperative pelvic IMRT has been shown to have decreased rates of myelosuppression in patients with gynecologic cancers treated with concurrent chemoradiation therapy, when compared to conventional 3D-CRT. However, there is limited data on how marrow sparing IMRT might impact tolerance in the setting of full-dose sequential chemotherapy and extended-field radiotherapy. A retrospective analysis of 158 patients with endometrial cancer treated with adjuvant sequential chemoradiation therapy with marrow sparing IMRT from 2008-2018 was performed. 146 of 158 patients received pre-IMRT chemotherapy, with 14 of 158 receiving post-IMRT chemotherapy. 63 patients were treated with extended field IMRT to include para-aortic lymph nodes, while 95 were treated with pelvic field IMRT including the entire common iliac region. Bone marrow was defined dosimetrically as the pelvic bone, bilateral femoral heads, and lower lumbosacral spine, with goal bone marrow V20 Gy < 80%. Myelosuppressive events were categorized using RTOG criteria. Linear regression analysis was used to assess for correlation between myelosuppression events and bone marrow dose. 157 of 158 (99.4%) patients completed EBRT as prescribed, with 1 discontinuing treatment due to acute GI toxicity. Median EBRT treatment time was 35 days (range 32-60 days). Total EBRT treatment time was 40 days or more in 17 patients (11%), with 4 patients having prolonged EBRT treatment time attributable to myelosuppression (range 42-57 days). All 158 patients had CBCs during treatment (median 4, range 1-8). Results for myelosuppressive events are detailed in the table below. Bone marrow V20 <80% was met in 118/158 (75%) of patients. Median bone marrow mean dose was 29.1 Gy (range 19.4-35.8 Gy). Median bone marrow V20 Gy was 73.9% (range 47.1-91.0%). Linear regression analysis did not reveal statistically significant associations between V20 Gy or mean bone marrow dose with grade 2 myelosuppression events. Grade 3 myelosuppression were rare events, with 2% incidence in pelvic field IMRT and 5% incidence in extended field IMRT. This is the largest series with marrow sparing IMRT in patients with endometrial cancer treated with sequential chemoradiation therapy, showing very low rates of grade III myelosuppression and 99.4% completion rate, with few treatment interruptions. With our goal bone marrow V20 Gy <80% dose met in the majority of patients, we were unable to determine a statistically significant relationship between myelosuppression events and V20 Gy or mean bone marrow dose.Abstract 2808; Table 1Grade 2 Anemia (Hgb<9.5-7.5)Grade 3 Anemia (Hgb <7.5)Grade 2 Neutropenia (ANC <1500-1000)Grade 3 Neutropenia (ANC <1000)Grade 2 Thrombocytopenia (PLT<75-50)Grade 3 Thrombocytopenia (PLT<50)Any Myelosuppression EventAny Grade 3 EventFrequency (n=158)20/158 (13%)0/158 (0%)33/158 (21%)4/158 (3%)8/158 (5%)1/158 (1%)53/158 (34%)5/158 (3%) Open table in a new tab

Optimal dose limitation strategy for bone marrow sparing in intensity-modulated radiotherapy of cervical cancer

BackgroundTo quantify the dosimetric parameters of different bone marrow sparing strategies and to determine the optimal strategy for cervical cancer patients undergoing postoperative intensity-modulated radiotherapy (IMRT).MethodsFifteen patients with cervical cancer were selected for analysis. The planning target volume (PTV) and the organs at risks (OAR) including small bowel, bladder, rectum, femoral heads, os coxae (OC), lumbosacral spine (LS) and bone marrow (BM) were contoured. For each patient, four IMRT plans with different strategies were generated, including one plan without BM as the dose-volume constraint, namely IMRT (N) plan, and three bone marrow sparing (BMS-IMRT) plans. The three BMS-IMRT plans used the BM, OC, OC and LS respectively, as the BM OAR, namely as IMRT (BM), IMRT (OC) and IMRT (OC + LS) plans. Dose volumes for the target and the OARs were compared using analysis of variance (ANOVA).ResultsCompared with IMRT (N) plans, the dose to the small bowel, bladder, rectum and femoral heads showed no increase in the three BMS-IMRT plans. However, the irradiated dose to BM, OC and LS significantly decreased. In particular, the mean dose of BM, OC and LS decreased by about 5Gy (p < 0.05) in IMRT (BM) plans while the average volume receiving ≥20, ≥30, ≥40Gy decreased by 7.1–24.2%. The LS volume receiving 40Gy showed the highest decrease (about 31.2%, p < 0.05) in IMRT (OC + LS) plans. On the other hand, in comparison with IMRT (BM), IMRT (OC) reduced the dose volume of to the OC, but increased the dose to LS while IMRT (OC + LS) plans reduced both the OC and the LS volume at all dose levels. Specifically, the V20 of OC and LS in the IMRT (OC + LS) plan decreased by 11.5 and 11.2%, respectively.ConclusionBy introducing the os coxae and lumbosacral spine as the dose–volume constraints, the IMRT plans exhibited the best sparing of the bone marrow without compromising the dose to surrounding normal structures. Therefore, we recommend adding the os coxae and lumbosacral spine as the BM OAR in such plans.

Tomotherapy as a neoadjuvant treatment for locally advanced esophageal cancer might increase bone marrow toxicity in comparison with intensity-modulated radiotherapy and volumetric-modulated arc therapy

This study compares dosimetric parameters in these following 3 neoadjuvant chemoradiotherapy (NCRT) methods in treating locally advanced esophagus cancer: helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). It is aimed to ascertain the efficient technique that kept high target coverage and availed the dose sparing of bone marrow (BM). This research collected data on 11 patients from October 2014 to June 2017 who received NCRT for pathologically confirmed esophageal cancer. The prescription doses to the planning target volume (PTV) were all given as 60 Gy (2 Gy per fraction, 5 days a week). Three physicists via Varian Eclipse Treatment Planning System and Accuray planning stations redesigned 5 radiotherapy plans (fixed 5-field IMRT, fixed 7-field IMRT, 2-arc VMAT, 3-arc VMAT, and TOMO) for each of the patients. At the end of the planning, we then appraised the dosimetric quality based on the PTV parameters and the doses to organs at risk (OARs). In the study VMAT reached the highest conformity index (CI; 2 arcs VMAT: 0.74 ± 0.10; 3 arcs VMAT: 0.78 ± 0.07; p< 0.05), and IMRT the lowest homogeneity index (HI; fivefields IMRT: 0.12 ± 0.03; sevenfields IMRT: 0.10 ± 0.02; p< 0.05). Besides, 7 fields IMRT (0.10 ± 0.02) achieved superior HI to that of 5 fields IMRT (0.12 ± 0.03, p< 0.01). TOMO (p< 0.05) and VMAT (p< 0.05) were both significantly superior to IMRT in terms of the dose to lung (V5, V10, V15, V20, and V30). These 5 radiation techniques were similar regarding the dose to heart (V5, V20, and V30), but IMRT (5 fields IMRT: 19.27 ± 5.33; 7 fields IMRT: 20.05 ± 4.19) significantly raised the dose to the V50 of the heart when compared to VMAT (2 arcs VMAT: 16.6 ± 5.68; 3 arcs VMAT: 15.04 ± 5.75; p< 0.05) and TOMO (15.05 ± 4.7, p< 0.05). VMAT reduced the dose to BM (V5, V10, V20, and V30) as compared to TOMO (p< 0.05) and IMRT (p< 0.05). The CI of VMAT was the supreme one in those of the techniques in this study, so was the HI of IMRT. VMAT also provided another advantage that it reduced the dose to the BM. TOMO ameliorated the dose sparing of the lung, but the dose that the BM absorbed from TOMO was of some concern about BM toxicity.

Alkylphospholipids are Signal Transduction Modulators with Potential for Anticancer Therapy.

Alkylphospholipids (APLs) are synthetically derived from cell membrane components, which they target and thus modify cellular signalling and cause diverse effects. This study reviews the mechanism of action of anticancer, antiprotozoal, antibacterial and antiviral activities of ALPs, as well as their clinical use. A literature search was used as the basis of this review. ALPs target lipid rafts and alter phospholipase D and C signalling cascades, which in turn will modulate the PI3K/Akt/mTOR and RAS/RAF/MEK/ERK pathways. By feedback coupling, the SAPK/JNK signalling chain is also affected. These changes lead to a G2/M phase cell cycle arrest and subsequently induce programmed cell death. The available knowledge on inhibition of AKT phosphorylation, mTOR phosphorylation and Raf down-regulation renders ALPs as attractive candidates for modern medical treatment, which is based on individualized diagnosis and therapy. Corresponding to their unusual profile of activities, their side effects result from cholinomimetic activity mainly and focus on the gastrointestinal tract. These aspects together with their bone marrow sparing features render APCs well suited for modern combination therapy. Although the clinical success has been limited in cancer diseases so far, the use of miltefosine against leishmaniosis is leading the way to better understanding their optimized use. Recent synthetic programs generate congeners with the increased therapeutic ratio, liposomal formulations, as well as diapeutic (or theranostic) derivatives with optimized properties. It is anticipated that these innovative modifications will pave the way for the further successful development of ALPs.

Radiation Nephropathy in a Nonhuman Primate Model of Partial-body Irradiation With Minimal Bone Marrow Sparing-Part 1: Acute and Chronic Kidney Injury and the Influence of Neupogen: Erratum.

Radiation Nephropathy in a Nonhuman Primate Model of Partial-body Irradiation With Minimal Bone Marrow Sparing-Part 1: Acute and Chronic Kidney Injury and the Influence of Neupogen: Erratum.