Adaptive radiation therapy of breast cancer by repeated imaging during irradiation

Breast cancer is the most frequent cancer among females and also a leading cause of cancer related mortality worldwide.A multimodality treatment approach may be utilized for optimal management of patients with combinations of surgery,radiation therapy(RT)and systemic treatment.RT composes an integral part of breast conserving treatment,and is typically used after breast conserving surgery to improve local control.Recent years have witnessed significant improvements in the discipline of radiation oncology which allow for more focused and precise treatment delivery.Adaptive radiation therapy(ART)is among the most important RT techniques which may be utilized for redesigning of treatment plans to account for dynamic changes in tumor size and anatomy during the course of irradiation.In the context of breast cancer,ART may serve as an excellent tool for patients receiving breast irradiation followed by a sequential boost to the tumor bed.Primary benefits of ART include more precise boost localization and potential for improved normal tissue sparing with adapted boost target volumes particularly in the setting of seroma reduction during the course of irradiation.Herein,we provide a concise review of ART for breast cancer in light of the literature.

Randomized control trial of a culturally adapted behavioral activation therapy for Muslim patients with depression in Pakistan

BACKGROUND Behavioral activation therapy(BA)is as effective as cognitive behavior therapy(CBT)in treating depression and can be delivered by practitioners with much less psychological training,making it particularly suitable for low resource settings.BA that is culturally adapted for Muslims(BA-M)is a culturally adapted form of BA that has been found acceptable and feasible for Muslims with depression in the United Kingdom and Turkey;however,this is the first time that its efficacy has been determined through a definitive randomized controlled trial.AIM To compare the effectiveness of BA-M with CBT for Muslim patients with depression in Pakistan.METHODS One hundred and eight patients were randomized 1:1 to treatment arms in a parallel-group randomized controlled trial in hospital or community sites in Lahore,Pakistan.Recruitment followed self-referral or referrals from clinicians,consultants or relevant professionals at each site.Four measures were recorded by blinded assessors:The patient health questionnaire-9(PHQ-9);the BA for depression scale short form(BADS-SF);symptom checklist-revised and the World Health Organization Quality-of-Life Brief Scale.All measures were recorded at baseline and post treatment;PHQ-9 and BADS-SF were also recorded at each session and at three month follow up.The primary analysis was to regress the PHQ-9 score after therapy upon the PHQ-9 score before therapy(baseline)and the type of therapy given,that is,analysis of covariance.In addition,analysis using PHQ-9 scores collected at each therapy session was employed in a 2-level regression model.RESULTS Patients in the BA-M arm experienced greater improvement in PHQ-9 score of 1.95 units compared to the CBT arm after adjusting for baseline values(P=0.006)The key reason behind this improvement was that patients were retained in therapy longer under BA-M,in which patients were retained for an average 0.75 sessions more than CBT patients(P=0.013).Patients also showed significant differences on physical(P<0.001),psychological(P=0.004)and social(P=0.047)domains of Quality of Life(QoL)at post treatment level,indicating an increased QoL in the BA-M group as compared to the treatment as usual group.Some baseline differences were noted in both groups for BA scores and two domains of QoL scale:Physical and environment,which might have influenced the results,though the BA-M group showed more improvement at completion of therapy.CONCLUSION Results proved the efficacy of BA-M in reducing symptoms for depressed patients in Pakistan,indicating BA-M is a promising treatment modality for depression in future,particularly in low resource settings.

An Evolutionary Approach for Personalized Therapy in Multiple Myeloma

Most patients with multiple myeloma (MM) respond well to initial therapy, but invariably relapse due to evolution of resistant phenotypes. Here we examine the evolutionary dynamics of proliferation of resistant MM phenotypes during therapy. By applying computational models to data from three clinical trials for newly diagnosed MM patients, we have quantified the size and level of chemoresistance of subpopulations within the tumor burden in 124 patients, prior to and during therapy. Subsequently, we used the computational models to explore an alternative strategy of “adaptive therapy” (AT), which includes defined treatment holidays, to improve the duration of “controlled disease” (CD). Simulations showed that AT could prolong CD in all three trials: 50.0% vs. 11.1% 50-month CD for a single agent approach in older adults (P = 0.0123), 80.4% vs. 58.8% 60-month CD for a multi-agent bortezomib based therapy (P = 0.0082), and 54.0% vs. 24.0% 60-month CD for a multi-agent lenalidomide based therapy (P < 0.0001). Increases in duration of CD resulted from the stabilization of tumor burden, which in turn would delay the growth of chemoresistant sub-populations in patients with partial (PR), or very good partial response (VGPR). These computational algorithms suggest that AT may provide an alternative and feasible therapeutic management strategy in MM.

Adaptive Dose-Compensation Technique for Image-Guided Radiotherapy of Prostate Cancer

Background: For image-guided radiotherapy(IGRT) of prostate cancer, the current standard is online image guidance which can effectively correct setup errors and inter-fraction rigid organ motion. However, planning margins are still necessary for deformation and intra-fraction motion. Objective: This paper aims to investigate an adaptive planning technique incorporating offline dose feedback to manage interfraction motion and residuals from online corrections. Methods:Repeated CT scans from 28 patients were studied. Online IG was simulated by matching center-of-mass of prostate. A seven-beam IMRT plan with zero margins was designed for each patient. Dose distribution at each fraction was evaluated based on actual target and OARs from that fraction. Cumulative dose was calculated using deformable registration and compared to initial plan. If deviation exceeded pre-defined 2% threshold in prostate D99 an adaptive planning technique called dose compensation was invoked, in which cumulative dose was fed back to the planning system and dose deficit was made up through boost radiation in future fractions through IMRT. Results: If 2% under-dose was allowed at the end of course, then 11 patients failed. If the same criteria was assessed at the end of each week(every 5 fractions), then 14 patients failed. The average dose deficit for these 14 patients was4.4%. They improved to 2% after weekly compensation. 10(out of 14) patients passed criterion after weekly dose compensation; 3 failed marginally; 1 failed significantly(10% deficit). A more aggressive compensation frequency(every 3 fractions) could reduce the dose deficit to the acceptable level for this patient. The doses to OARs were not significantly different from online IG only without dose compensation.Conclusion: We demonstrated an offline dose compensation technique in prostate IGRT which can effectively account for residual uncertainties uncorrectable in online IG. Dose compensation allows further margin reduction and critical organs sparing.

Stereotactic ablative radiotherapy for hepatocellular carcinoma

Patients with hepatocellular carcinoma(HCC)often present with underlying liver disease and significant comorbidities,limiting treatment tolerance.With the development of improved toxicity models and highly conformal radiation delivery systems,external beam radiotherapy has become a valuable treatment option for liver cancer.Using cutting edge technology,stereotactic ablative radiotherapy(SABR)allows for the delivery of ablative doses in few fractions while sparing uninvolved liver tissue.This approach permits dose escalation and precise tumor targeting with minimal risk of radiation induced liver disease.This review clarifies SABR's role alongside liver-directed treatments such as radiofrequency ablation,transarterial radioembolization,and transarterial chemoembolization in the management of HCC.It also examines the promising potential of SABR combined with immunotherapy to treat advanced HCC.

Comparison of Volumetric and Dosimetric Variations in Nasopharyngeal Carcinoma during Intensity-modulated Radiation Therapy with and without Neoadjuvant Chemotherapy

Objective Patients with nasopharyngeal carcinoma(NPC)undergoing intensity-modulated radiation therapy(IMRT)may experience significant volumetric and dosimetric variations throughout the treatment course.However,neoadjuvant chemotherapy may reduce the extent of these variations.This study was carried out to evaluate volumetric and dosimetric changes in target volumes and organs at risk(OARs)during IMRT in patients with locally advanced NPC who received concurrent chemoradiotherapy(CCRT)alone or in combination with neoadjuvant chemotherapy(NACT).Methods 35 NPC patients were recruited for this study and divided into the NACT(n=15)and CCRT(n=20)groups.Computed tomography(CT)scans were performed before neoadjuvant chemotherapy,before IMRT,before the 24 th fraction of IMRT,and after treatment.The original plan(plan 0)was based on CT images collected before IMRT.Hybrid plan 1(plan 1)and hybrid plan 2(plan 2)were generated by applying the beam configurations of plan0 to the CT scans collected before the 24 th fraction of IMRT and after treatment.Volumetric and dosimetric variations were assessed by comparing the results of plan 0 with those of plan 1 and plan 2.Results In the NACT group,compared with that in plan 0,the primary gross tumor volume(GTVnx)decreased by 33.2%±18.4%and 50.5%±12.6%in plan1 and plan 2,respectively.In the CCRT group,the corresponding reduction rates in plan 1 and plan 2 were 49.4%±8.0%and 77.8%±28.1%,respectively.The volume decrease rates in the NACT group were less than those in the CCRT group(P<0.001).In the NACT group,compared with that of plan0,the dose to 95%of the volume(D95)for the planning target volume of the primary tumor(PTVnx)decreased by 1.0%±0.7%and 0.6%±0.6%in plan 1 and plan 2,respectively.In the CCRT group,the corresponding decrease rates in plan 1 and plan 2 were 4.2%±3.8%and 6.1%±6.3%,respectively.The decrease rate of D95 for PTVnx in the NACT group was less than that in the CCRT group(P<0.001).Similar results among the plans were found in terms of D99,Dmean,V93 for PTVnxand PTVnd,and Dmeanfor the parotid glands.Conclusion Neoadjuvant chemotherapy reduces the extent of volumetric and dosimetric variations in target volumes and OARs during IMRT and,thus,helps achieve better target volume coverage,protects adjacent important structures,and minimizes unnecessary replanning during radiotherapy.