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Background: Female survivors treated with thoracic radiation therapy (RT) for childhood cancer experience increased risks of breast cancer (BC). There are currently no data quantifying the potential mortality gains of early BC screening among such survivors.Methods: A mathematical model of BC development was used to evaluate the marginal benefit of early-initiated screening of female survivors of adolescent Hodgkin's lymphoma (HL) starting at age 25 years on BC mortality compared with screening initiated at age 40 years. Sensitivity analyses were performed to evaluate the robustness of the estimates over a plausible range of conditions.Results: For survivors treated at age 15 years, the absolute risk of BC mortality by age 75 years was predicted to decrease from 16.65% with no early screening to 16.28% (annual mammography), 15.40% (annual MRI), 15.38% (same-day annual mammography and MRI), and 15.37% (alternating mammography and MRI every six months). Approximately 80 patients would need to be invited to MRI-based screening to prevent one BC death. In sensitivity analyses, the number needed to invite to MRI-based screening to prevent one BC death ranged from 71 to 333. Combinations of MRI plus mammography were predicted to produce 99.52 false positives per 1000 screenings done between age 25 to 39 years.Conclusions: These findings are the first to indicate that early MRI-based screening should reduce BC mortality among women treated with RT for adolescent HL. The magnitude of this benefit is superior to that described for other accepted screening indications although MRI can produce a substantial rate of false-positive results. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. Methods and Materials: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. Results: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). Conclusions: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors. [Copyright &y& Elsevier]

The article offers information on a population-based study which assessed the follow-up care given to a cohort of Hodgkin's lymphoma (HL) survivors. Particularly, the researchers identified the scope to which routine imaging, standard healthcare interventions, and HL-specific screening guidelines were used. Data analyzed were from patients diagnosed with HL in Ontario from 1992 to 2000. A discussion on the research findings is detailed. It concludes that many survivors were not given the recommended cancer screening interventions.

Purpose: To describe the patterns of follow-up care provided to a population-based cohort of breast cancer survivors, and to assess factors associated with adherence to guidelines on follow- up care. Patients and Methods: We conducted a retrospective longitudinal study of all women with surgically treated breast cancer who were without evidence of recurrence, advanced breast cancer, or new primary cancer and were diagnosed in Ontario, Canada, within a 2-year period (n = 11,219). They were followed for 5 years. The cohort was identified through the Ontario Cancer Registry, and individuals were linked across population-based administrative health databases. Frequency of and adherence to guideline recommendations for oncologist and primary care physician (PCP) visits; surveillance imaging for metastatic disease; and surveillance mammograms by year from diagnosis, age group, and income quintile were analyzed. Factors associated with adherence to guideline recommendations were analyzed. Results: Most women saw both oncologists and PCPs in each follow-up year. Approximately two thirds had surveillance mammograms in each follow-up year. Overall, two thirds had either fewer or greater than recommended oncology visits, one quarter had fewer than recommended surveillance mammograms, and half had greater than recommended surveillance imaging for metastatic disease. Conclusion: This population-based study shows substantial variation in adherence to guideline recommendations, with both overuse and underuse of surveillance visits and tests. Most importantly, a substantial proportion are receiving more than recommended imaging for metastatic disease but fewer than recommended mammograms for detection of local recurrence or new primary cancer, for which effective intervention is possible. [ABSTRACT FROM AUTHOR]

The article discusses a study which estimated the second cancer risks in patients who have undergone contemporary radiation therapy (RT) for Hodgkin lymphoma. The study developed three RT plans for 37 patients. It found that contemporary involved-field RT can reduce the risk for secondary breast and lung cancer.

Purpose: Patients with chemotherapy-resistant lymphoma have rapidly progressive disease and a poor prognosis. Local symptoms are treated with radiotherapy (RT) for local control. We have reviewed local control and toxicity in patients treated with hyperfractionated accelerated RT. Methods and Materials: A total of 34 patients received hyperfractionated RT between 1997 and 2003. The radiation dose was 39.9–40.5 Gy in 30 fractions. The median treatment time was 22 days with twice-daily involved-field RT. The median follow-up was 4.4 years. Response was assessed <3 months after RT and was classified as a complete response, a complete response-unconfirmed, a partial response, or no response. Local control was defined as maintenance of local complete response, complete response-unconfirmed, or lack of local progression with a partial response. Recurrence or progression outside the RT volume was regarded as distant disease. Results: The median age was 53 years; 20 patients were men and 14 were women. The initial diagnosis was Stage I–II in 56% and Stage III–IV in 44%. The disease bulk was ≥10 cm in 35% (n = 12). The histologic features at diagnosis were follicular in 11 (Grade 1 in 4, Grade 2 in 3, and Grade 3 in 4), diffuse large B-cell in 14, peripheral T-cell lymphoma in 2, Burkitt-like in 1, mantle cell in 2, natural killer cell in 2, plasmacytoma/lymphoma in 1, and T-cell lymphoblastic in 1. The initial treatment was chemotherapy in 32 patients (94%); 71% were refractory to initial chemotherapy and 29% developed a relapse after an initial response. The RT response was complete in 24% (n = 8), complete, unconfirmed in 26% (n = 9), partial in 47% (n = 16), and none in 3% (n = 1). The local control rate was 73% at 1, 2, and 3 years. Grade 1 dermatitis was the most common side effect. Conclusion: Hyperfractionated RT provided good local control and was well tolerated. This encouraging result requires additional study with comparison to conventional fractionation regimens. [Copyright &y& Elsevier]

: PurposeTo examine the impact of extranodal chest wall and lung invasion on the prognosis of patients with clinical Stage I–II Hodgkin''s lymphoma treated with combined modality therapy.: Methods and materialsThe outcome of 324 patients with clinical Stage I–II Hodgkin''s lymphoma treated with combined modality therapy between 1981 and 1996 was analyzed. Twenty-two patients had chest wall invasion and 40 had invasion of lung parenchyma. The chemotherapy regimens used were ABVD in 182 patients (56%), MOPP/ABV(D) in 45 (14%), MOPP in 86 (27%), and other chemotherapy regimens in 11 patients (3%). This was followed by mantle/mediastinal radiotherapy (RT) in 163 patients (50%), extended-field RT in 135 patients (42%), and infradiaphragmatic RT in 26 patients (8%). The impact of chest wall and lung invasion on local relapse, disease-free survival, cause-specific survival, and overall survival was examined.: ResultsAfter a median follow-up of 8.3 years, the 5-year cause-specific and overall survival rate of the entire cohort was 93% and 90%, respectively. Compared with patients with no extranodal involvement, patients with chest wall invasion had significantly worse local control (89% vs. 68%, p = 0.005), disease-free survival (84% vs. 59%, p = 0.016), and cause-specific survival (94% vs. 86%, p = 0.009). Overall survival was also worse among patients with chest wall invasion, but not significantly so (90% vs. 82%, p = 0.10). Among the 16 patients with chest wall invasion but without lung invasion, 7 progressed during treatment or relapsed, 6 with local failure (crude relapse rate 44%, 95% confidence interval [CI] 19–68%), and 5 died (crude death rate 31%, 95% CI 9–54%). After adjusting for other significant prognostic factors, patients with chest wall invasion had significantly worse local control (hazard ratio 2.8, 95% CI 1.2–6.3), disease-free survival (hazard ratio 2.3, 95% CI 1.1–4.8), and cause-specific survival (hazard ratio 2.8, 95% CI 1.1–6.8). Lung invasion was not significantly associated with any of the outcomes assessed.: ConclusionChest wall invasion is an adverse prognostic factor among clinical Stage I–II Hodgkin''s lymphoma patients treated with combined modality therapy, although we did not find a worse outcome for patients with lung invasion. Efforts to reduce treatment intensity in these patients should be undertaken with caution, recognizing their increased risk of local relapse. [Copyright &y& Elsevier]

Background: Postoperative mortality after some types of cancer surgery is inversely related to the number of operations performed at a hospital (i.e., hospital volume). This study assessed the association of hospital volume with colostomy rates and survival for patients with rectal cancer in a large representative cohort identified from the California Cancer Registry. Methods: We identified 7257 patients diagnosed from January 1, 1994, through December 31, 1997, with stage I-III rectal cancer who underwent surgical resection. Registry data were linked to hospital discharge abstracts and ZIP-code-level data from the 1990 U.S. Census. Associations of hospital volume with permanent colostomy and 30-day mortality were assessed with the Mantel-Haenszel trend test and logistic regression. Overall survival was examined with the Kaplan-Meier method and a multivariable Cox proportional hazards model. Multivariable analyses adjusted for demographic and clinical variables and patient clustering within hospitals. All tests of statistical significance were two-sided. Results: In unadjusted analyses across decreasing quartiles of hospital volume, we observed statistically significant increases in colostomy rates (29.5%, 31.8%, 35.2%, and 36.6%; P<.001) and in 30-day postoperative mortality (1.6%, 1.6%, 2.9%, and 4.8%; P<.001) and a decrease in 2-year survival (83.7%, 83.2%, 80.9%, and 76.6%; P<.001). The adjusted risks of permanent colostomy (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.10 to 1.70), 30-day mortality (OR = 2.64, 95% CI = 1.41 to 4.93), and 2-year mortality (hazard ratio = 1.28, 95% CI = 1.15 to 1.44) were greater for patients at hospitals in the lowest volume quartile than for patients at hospitals in the highest volume quartile. Stratification by tumor stage and comorbidity index did not appreciably affect the results. Adjusted colostomy rates varied statistically significantly (P<.001) among individual hospitals independent of volume.... [ABSTRACT FROM AUTHOR]

While the management and prognosis of colorectal cancer are largely dependent on clinical features such as tumor stage, there is considerable variation in treatment and outcome not explained by traditional prognostic factors. To guide efforts by researchers and health-care providers to improve quality of care, we review studies of variation in treatment and outcome by patient and provider characteristics. Surgeon expertise and case volume are associated with improved tumor control, although surgeon and hospital factors are not associated consistently with perioperative mortality or long-term survival. Some studies indicate that patients are less likely to undergo permanent colostomy if they are treated by high-volume surgeons and hospitals. Differences in treatment and outcome of patients managed by health maintenance organizations or fee-for-service providers have not generally been found. Older patients are less likely to receive adjuvant therapy after surgery, even after adjustment for comorbid illness. In the United States, black patients with colorectal cancer receive less aggressive therapy and are more likely to die of this disease than white patients, but cancer-specific survival differences are reduced or eliminated when black patients receive comparable treatment. Patients of low socioeconomic status (SES) have worse survival than those of higher SES, although the reasons for this discrepancy are not well understood. Variations in treatment may arise from inadequate physician knowledge of practice guidelines, treatment decisions based on unmeasured clinical factors, or patient preferences. To improve quality of care for colorectal cancer, a better understanding of mechanisms underlying associations between patient and provider characteristics and outcomes is required. [ABSTRACT FROM AUTHOR]

Pediatric Normal Tissue Effects in the Clinic (PENTEC) is an international multidisciplinary effort that aims to summarize normal-tissue toxicity risks based on published dose-volume data from studies of children and adolescents treated with radiation therapy (RT) for cancer. With recognition that children are uniquely vulnerable to treatment-related toxic effects, our mission and challenge was to assemble our group of physicians (radiation and pediatric oncologists, subspecialists), physicists with clinical and modeling expertise, epidemiologists, and other scientists to develop evidence-based radiation dosimetric guidelines, as affected by developmental status and other factors (eg, other cancer therapies and host factors). These quantitative toxicity risk estimates could serve to inform RT planning and thereby improve outcomes. Tandem goals included the description of relevant medical physics issues specific to pediatric RT and the proposal of dose-volume outcome reporting standards to inform future studies. We created 19 organ-specific task forces and methodology to unravel the wealth of data from heterogeneous published studies. This report provides a high-level summary of PENTEC's genesis, methods, key findings, and associated concepts that affected our work and an explanation of how our findings may be interpreted and applied in the clinic. We acknowledge our predecessors in these efforts, and we pay homage to the children whose lives informed us and to future generations who we hope will benefit from this additional step in our path forward. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy. In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores. The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P =.03 and.007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P <.001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P <.001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores. Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma. [ABSTRACT FROM AUTHOR]

Purpose: The Children's Oncology Group protocol AHOD0831, for pediatric patients with high-risk classical Hodgkin lymphoma (cHL), used response-adapted radiation fields, rather than larger involved-field radiation therapy (IFRT) that were historically used. This retrospective analysis of patterns of relapse among patients enrolled in the study was conducted to study the potential effect of a reduction in RT exposure.Methods and Materials: From December 2009 to January 2012, 164 eligible patients under 22 years old with stage IIIB (43%) and stage IVB (57%) enrolled on AHOD0831. All patients received 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Those patients with a slow early response (SER) after the first 2 ABVE-PC courses were nonrandomly assigned to 2 intensification cycles with ifosfamide/vinorelbine before the final 2 ABVE-PC cycles. Response-adapted RT (21 Gy) was prescribed to initial areas of bulky disease and SER sites. Rapid early response (RER) sites without bulk were not targeted. Imaging studies at the time of progression or relapse were reviewed centrally for this retrospective analysis. Relapses were characterized with respect to site (initial, new, or both; and initial bulk or initial nonbulk), initial chemotherapy response, and radiation field (in-field, out-of-field, or both).Results: Of the entire cohort, 140 patients were evaluable for the patterns of failure analyses. To investigate the pattern of failure, this analysis focuses on 23 patients who followed protocol treatment and suffered relapses at a median 1.05 years with 7.97-year median follow-up time. These 23 patients (11 RER and 12 SER) experienced a relapse in 105 total sites (median, 4; range, 1-11). Of the 105 relapsed sites, 67 sites (64%) occurred within an initial site of involvement, with 12 of these 67 sites (18%) at an initial site of bulky disease and 63 of these 67 relapses (94%) occurring in sites that were not fluorodeoxyglucose (FDG)-avid after 2 cycles of ABVE-PC (PET2-negative). Of the 105 relapsed sites, 34 sites (32%) occurred in a new site of disease (that would not have been covered by RT); and, overall, only 4 of 140 patients (2.8%) (occurring in 3 RER and 1 SER) experienced isolated out-of-field relapses that would have been covered by historical IFRT.Conclusions: For a cohort of high-risk patients with cHL patients, most failures occurred in nonbulky, initially involved sites, largely due to response-based consolidation RT delivered to patients with bulky disease. In this analysis, we discovered low rates of failures outside of these modern risk-adapted radiation treatment volumes. Also, FDG uptake on PET2 did not identify most relapse sites. [ABSTRACT FROM AUTHOR]

The authors comment on the study that investigates the developments in evidence-based screening of children cancer survivors.

The optimal salvage chemotherapy regimen (SC) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prior to autologous stem cell transplant remains unclear. Moreover, although chimeric antigen receptor T cell (CAR-T) therapies were recently approved for primary refractory DLBCL, head-to-head comparisons are lacking. We searched MEDLINE, EMBASE and CENTRAL to July 2022, for randomized trials that enrolled adult patients with R/R DLBCL and performed network meta-analyses (NMA) to assess the efficacy of SC and CAR-T therapies. NMA of SC (6 trials, 7 regimens, n = 1831) indicated that rituximab with gemcitabine, dexamethasone, cisplatin (R-GDP) improved OS and PFS over compared regimens. NMA of 3 CAR-T trials (n = 865) indicated that both axi-cel and liso-cel improved PFS over standard of care, with no difference in OS. Our results indicate that R-GDP may be preferred for R/R DLBCL over other SC compared. Longer follow-up is required for ongoing comparative survival analysis as data from CAR-T trials matures. [ABSTRACT FROM AUTHOR]

We investigated the effects of central review of the interim fluorodeoxyglucose−positron emission tomography/computed tomography (FDG-PET/CT) scan response (iPET) assessment on treatment allocation in the risk-based, response-adapted, Children's Oncology Group study AHOD1331 (ClinicalTrials.gov identifier: NCT02166463) for pediatric patients with high-risk Hodgkin lymphoma. Per protocol, after 2 cycles of systemic therapy, patients underwent iPET, with visual response assessment by 5-point Deauville score (DS) at their treating institution and a real-time central review, with the latter considered the reference standard. An area of disease with a DS of 1 to 3 was considered a rapid-responding lesion, whereas a DS of 4 to 5 was considered a slow-responding lesion (SRL). Patients with 1 or more SRLs were considered iPET positive, whereas patients with only rapid-responding lesions were considered iPET negative. We conducted a predefined exploratory evaluation of concordance in iPET response assessment between institutional and central reviews of 573 patients. The concordance rate was evaluated using the Cohen κ statistic (κ > 0.80 was considered very good agreement and κ > 0.60-0.80, good agreement). The concordance rate (514 of 573 [89.7%]) had a κ of 0.685 (95% CI, 0.610-0.759), consistent with good agreement. In terms of the direction of discordance, among the 126 patients who were considered iPET positive by institutional review, 38 (30.2%) were categorized as iPET negative by central review, preventing overtreatment with radiation therapy. Conversely, among the 447 patients who were considered iPET negative by institutional review, 21 patients (4.7%) were categorized as iPET positive by the central review and would have been undertreated without radiation therapy. Central review is integral to PET response−adapted clinical trials for children with Hodgkin lymphoma. Continued support of central imaging review and education about DS are needed. [ABSTRACT FROM AUTHOR]

In this article the authors comment on randomized trials which compared chemotherapy versus combined modality therapy in non-Hodgkin lymphoma patients. The authors argue that the studies are limited by the retrospective study designs despite attempts in controlling prognostic differences between irradiated and non-irradiated cohorts. Also, there is a need to identify subgroup of patients that will benefit from radio therapy (RT) in the rituximab era while adoption modern RT techniques.

The article presents the authors' comments on various aspects of proton therapy for Hodgkin lymphoma, with reference to a case report published within this issue. It is stated that the traditional treatments for Hodgkin lymphoma (HL) can increase the risk of heart disease among long-term survivors. Proton therapy allows reductions in radiation therapy-related toxicity. It is stated that the case report illustrates the role of proton therapy to reduce late effects of radiation therapy (RT).

The outcome for children and adolescents with low risk Hodgkin lymphoma ( HL) is excellent, with event-free survival >85% and overall survival >95%. Historically, however, treatment has come at the cost of significant long-term toxicity from chemotherapy, radiation or a combination of these. Recent treatment strategies have focused on maintaining high event-free and overall survival while minimizing the use of therapy associated with late effects. The strategies used to achieve this vary greatly among paediatric cooperative groups and there is no one standard treatment for children with low risk HL. This review summaries recent clinical trials in paediatric low risk HL and addresses some of the important considerations when comparing trials, including differences in the definition of low risk HL, differences in outcome among histological subtypes and varying approaches to reduce or eliminate radiation therapy. Recommendations are provided for the treatment of children with low risk HL outside the setting of a clinical trial. [ABSTRACT FROM AUTHOR]

Purpose: Numerous studies have implicated elevated second cancer risks as a result of radiation therapy. Our aim in this paper was to contribute to an understanding of the effects of radiation quality on second cancer risks. In particular, we developed a biologically motivated model to study the effects of linear energy transfer (LET) of charged particles (including protons, alpha particles and heavy ions Carbon and Neon) on the risk of second cancer. Materials and methods: A widely used approach to estimate the risk uses the so-called initiation-inactivation-repopulation model. Based on the available experimental data for the LET dependence of radiobiological parameters and mutation rate, we generalized this formulation to include the effects of radiation quality. We evaluated the secondary cancer risks for protons in the clinical range of LET, i.e., around 4-10 (KeV/μm), which lies in the plateau region of the Bragg peak. Results: For protons, at a fixed radiation dose, we showed that the increase in second cancer risks correlated directly with increasing values of LET to a certain point, and then decreased. Interestingly, we obtained a higher risk for proton LET of 10 KeV/μm compared to the lower LET of 4 KeV/μm in the low dose region. In the case of heavy ions, the risk was higher for Carbon ions than Neon ions (even though they have almost the same LET). We also compared protons and alpha particles with the same LET, and it was interesting to note that the second cancer risks were higher for protons compared to alpha particles in the low-dose region. Conclusion: Overall, this study demonstrated the importance of including LET dependence in the estimation of second cancer risk. Our theoretical risk predictions were noticeably high; however, the biological end points should be tested experimentally for multiple treatment fields and to improve theoretical predictions. [ABSTRACT FROM AUTHOR]

• Children may be treated with RT awake using audiovisual distraction. • 65 children were enrolled to evaluate intrafraction movement using cone beam CT. • 99 % of treatments to the head-and-neck had <3 mm movement. • 97 % of treatments to other sites had <5 mm movement. • Audiovisual distraction is an effective method of avoiding anaesthesia in children. Children who require radiation therapy (RT) should ideally be treated awake, without anaesthesia, if possible. Audiovisual distraction is a known method to facilitate awake treatment, but its effectiveness at keeping children from moving during treatment is not known. The aim of this study was to evaluate intrafraction movement of children receiving RT while awake. In this prospective study, we measured the intrafraction movement of children undergoing treatment with fractionated RT, using pre- and post-RT cone beam CT (CBCT) with image matching on bony anatomy. Study CBCTs were acquired at first fraction, weekly during RT, and at last fraction. The primary endpoint was the magnitude of vector change between the pre- and post-RT scans. Our hypothesis was that 90 % of CBCT acquisitions would have minimal movement, defined as <3 mm for head-and-neck (HN) treatments and <5 mm for non-HN treatments. A total of 65 children were enrolled and had evaluable data across 302 treatments with CBCT acquisitions. Median age was 11 years (range, 2–18; 1st and 3rd quartiles 7 and 14 years, respectively). Minimal movement was observed in 99.4 % of HN treatments and 97.2 % of non-HN treatments. The study hypothesis of >90 % of evaluations having minimal movement was met. Children who were age >11 years moved less at initial evaluation but tended to move more as a course of radiation progressed, as compared to children who were younger. Children receiving RT with audiovisual distraction while awake had small magnitudes of observed intrafraction movement, with minimal movement in >97 % of observed RT fractions. This study validates methods of anaesthesia avoidance using audiovisual distraction for selected children. [ABSTRACT FROM AUTHOR]

Purpose: High-quality radiotherapy (RT) planning for children and young adults with primary brain tumours is essential to minimize the risk of late treatment effects. The feasibility of using automated machine-learning (ML) to aid RT planning in this population has not previously been studied.Methods and Materials: We developed a ML model that identifies learned relationships between image features and expected dose in a training set of 95 patients with a primary brain tumour treated with focal radiotherapy to a dose of 54 Gy in 30 fractions. This ML method was then used to create predicted dose distributions for 15 previously-treated brain tumour patients across two institutions, as a testing set. Dosimetry to target volumes and organs-at-risk (OARs) were compared between the clinically-delivered (human-generated) plans versus the ML plans.Results: The ML method was able to create deliverable plans in all 15 patients in the testing set. All ML plans were generated within 30 min of initiating planning. Planning target volume coverage with 95% of the prescription dose was attained in all plans. OAR doses were similar across most structures evaluated; mean doses to brain and left temporal lobe were lower in ML plans than manual plans (mean difference to left temporal, - 2.3 Gy, p = 0.006; mean differences to brain, - 1.3 Gy, p = 0.017), whereas mean doses to right cochlea and lenses were higher in ML plans (+ 1.6-2.2 Gy, p < 0.05 for each).Conclusions: Use of an automated ML method to aid RT planning for children and young adults with primary brain tumours is dosimetrically feasible and can be successfully used to create high-quality 54 Gy RT plans. Further evaluation after clinical implementation is planned. [ABSTRACT FROM AUTHOR]

• Uncertainties in retrospectively reconstructed cardiac doses are moderate. • The uncertainties had little effect on dose–response relationships for cardiac risk. • Using radiation dose–response relationships to predict cardiac risks is appropriate. Radiation-related heart disease (RRHD) can occur many decades after thoracic radiotherapy for Hodgkin lymphoma (HL) or childhood cancer (CC). To quantify the likely risk of RRHD for patients treated today, dose–response relationships derived from patients treated in previous decades are used. Publications presenting these dose–response relationships usually include estimates of uncertainties in the risks but ignore the effect of uncertainties in the reconstructed cardiac doses. We assessed the systematic and random uncertainties in the reconstructed doses for published dose–response relationships for RRHD risk in survivors of HL or CC. Using the same reconstruction methods as were used in the original publications, we reconstructed mean heart doses and, wherever possible, mean left-ventricular doses for an independent case-series of test patients. These patients had known, CT-based, cardiac doses which were compared with the reconstructed doses to estimate the magnitude of the uncertainties and their effect on the dose–response relationships. For all five reconstruction methods the relationship between reconstructed and CT-based doses was linear. For all but the simplest reconstruction method, the dose uncertainties were moderate, the effect of the systematic uncertainty on the dose–response relationships was less than 10%, and the effects of random uncertainty were small except at the highest doses. These results increase confidence in the published dose–response relationships for the risk of RRHD in HL and CC survivors. This may encourage doctors to use these dose–response relationships when estimating individualised risks for patients—an important aspect of personalising radiotherapy treatments today. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors (CCS) are at increased risk of developing colorectal cancer (CRC) compared to the general population, especially those previously exposed to abdominal or pelvic radiation therapy (APRT). However, the benefits and costs of CRC screening in CCS are unclear. In this study, we evaluated the cost-effectiveness of early-initiated colonoscopy screening in CCS.Methods: We adjusted a previously validated model of CRC screening in the US population (MISCAN-Colon) to reflect CRC and other-cause mortality risk in CCS. We evaluated 91 colonoscopy screening strategies varying in screening interval, age to start, and age to stop screening for all CCS combined and for those treated with or without APRT. Primary outcomes were CRC deaths averted (compared to no screening) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per life-years gained (LYG) was used to determine the optimal screening strategy.Results: Compared to no screening, the US Preventive Services Task Force's average risk screening schedule prevented up to 73.2% of CRC deaths in CCS. The optimal strategy of screening every 10 years from age 40 to 60 years averted 79.2% of deaths, with ICER of $67 000/LYG. Among CCS treated with APRT, colonoscopy every 10 years from age 35 to 65 years was optimal (CRC deaths averted: 82.3%; ICER: $92 000/LYG), whereas among those not previously treated with APRT, screening from age 45 to 55 years every 10 years was optimal (CRC deaths averted: 72.7%; ICER: $57 000/LYG).Conclusions: Early initiation of colonoscopy screening for CCS is cost-effective, especially among those treated with APRT. [ABSTRACT FROM AUTHOR]

Summary: The AHOD0831 study for paediatric patients with high risk Hodgkin lymphoma tested a response‐based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. Patients (Stage IIIB/IVB) received two cycles of ABVE‐PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE‐PC. Slow early responders (SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE‐PC. Radiotherapy was administered to sites of initial bulk and/or SER. By intent‐to‐treat analysis, 4‐year second event‐free survival (EFS; freedom from second relapse or malignancy) was 91·9% [95% confidence interval (CI): 86·1–95·3%], below the projected baseline of 95% (P = 0·038). Five‐year first EFS and overall survival (OS) rates are 79·1% (95% CI: 71·5–84·8%) and 95% (95% CI: 88·8–97·8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy‐proven, 5 with progressive disease or later relapses). Although this response‐directed approach did not reach the ambitiously high pre‐specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced meningioma is a known late effect of cranial radiation therapy. Cranial magnetic resonance imaging (MRI) can detect small meningiomas, but its potential value as a screening tool is unknown.Methods and Materials: MRI was used to screen asymptomatic survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy ≥10 years previously. The incidence of radiation-induced meningioma and outcomes of this group were compared with a historical cohort of survivors with the same exposure who underwent imaging only to investigate clinical signs or symptoms.Results: One hundred seventy-six childhood leukemia survivors were included in this study: 70 in the screening group and 106 unscreened. Screening MRI was performed a median of 25 years after radiation therapy and detected meningioma in 15 (21.4%). In the unscreened group, 17 patients (16.0%) had neurologic symptoms leading to an MRI a median interval of 24 years after radiation therapy, 9 of whom (8.5%) were diagnosed with meningioma. There was no significant difference between screened versus unscreened patients in the size of meningioma (mean diameter, 1.6 cm vs 2.6 cm; P = .13), meningioma incidence (7.4% vs 4.0% at 25 years; P = .19), or extent of resection. Three patients had persistent neurologic symptoms in the unscreened group versus none among screened patients (P = .28).Conclusions: Screening MRI was able to detect small meningiomas that were not clinically apparent; however, we could not demonstrate a significant improvement in the chance of total resection or a significant decrease in morbidity. A larger sample could clarify potential reduction in neurologic sequelae associated with screening. [ABSTRACT FROM AUTHOR]

Summary: We developed a novel simulation model integrating multiple data sets to project long‐term outcomes with contemporary therapy for early‐stage Hodgkin lymphoma (ESHL), namely combined modality therapy (CMT) versus chemotherapy alone (CA) via 18F‐fluorodeoxyglucose positron emission tomography response‐adaption. The model incorporated 3‐year progression‐free survival (PFS), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35‐year probability of LEs. Furthermore, we generated estimates for quality‐adjusted life years (QALYs) and unadjusted survival (life years, LY) and used model projections to compare outcomes for CMTversusCA for two index patients. Patient 1: a 25‐year‐old male with favourable ESHL (stage IA); Patient 2: a 25‐year‐old female with unfavourable ESHL (stage IIB). Sensitivity analyses assessed the impact of alternative assumptions for LE probabilities. For Patient 1, CMT was superior to CA (CMT incremental gain = 0·11 QALYs, 0·21 LYs). For Patient 2, CA was superior to CMT (CA incremental gain = 0·37 QALYs, 0·92 LYs). For Patient 1, the advantage of CMT changed minimally when the proportion of severe LEs was reduced from 20% to 5% (0·15 QALYs, 0·43 LYs), whereas increasing the severity proportion for Patient 2's LEs from 20% to 80% enhanced the advantage of CA (1·1 QALYs, 6·5 LYs). Collectively, this detailed simulation model quantified the long‐term impact that varied host factors and alternative contemporary treatments have in ESHL. [ABSTRACT FROM AUTHOR]

Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early- and advanced-stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood to maximize our success in treating these patients. The complexity of treating relapsed or refractory HL derives from the spectrum of primary treatment approaches currently in use that creates heterogeneity in both treatment exposure and the potential toxicities of salvage therapy. Patients can have relapsed or refractory disease after limited or aggressive primary therapy (with or without radiation therapy), at early or delayed time points, with limited or extensive disease volumes, and with varying degrees of residual morbidity from primary therapy. Their response to salvage systemic therapy can be partial or complete, and the use of consolidative stem cell transplantation is variably applied. New biologics and immunotherapeutic approaches have broadened but also complicated salvage treatment approaches. Through all of this, radiation therapy remains an integral component of treatment for many patients, but it must be used effectively and judiciously. The purpose of this review is to describe the different treatment scenarios and provide guidance for radiation dose, volume, and timing in patients with relapsed or refractory HL. [ABSTRACT FROM AUTHOR]

Background: To measure the clinical impact of pretreatment fludeoxyglucose positron emission tomography/computed tomography (PET/CT) on the staging and management of apparent limited stage indolent lymphoma being considered for curative radiation therapy.Methods: We conducted a prospective multicenter registry study that included 197 patients accrued between May 1, 2012, and December 31, 2015. Pre-PET/CT stage, determined by clinical and CT data, was documented. If pre-PET/CT stage was indeterminate, a stage was assigned to the patient by the referring oncologist according to best clinical judgment and treatment intent. After PET/CT, revised stage and planned management were recorded and compared with data on actual treatment received available through provincial databases (n = 155).Results: PET/CT resulted in the upstaging of 47 (23.9%) patients with presumed limited stage disease (stage I-II) to advanced stage disease (stage III-IV) (P < .0001). Ten (5.1%) patients were downstaged by PET/CT, 4 of whom migrated from advanced to limited stage disease. Twenty-eight (14.2%) patients with a specific pre-PET/CT stage had equivocal PET/CT findings that required further evaluation to confirm disease extent. After PET/CT, 95 (61.3%) patients were planned to receive active treatment. Of the 59 patients planned for radiotherapy alone post-PET/CT, 34 (57.6%) received this treatment (P = .002), and nearly 80% of them (n = 27) had confirmed limited stage disease.Conclusion: PET/CT has a significant impact on staging and management in patients with apparent limited stage indolent lymphoma who are being considered for curative radiotherapy. PET/CT should be routinely incorporated into the workup of these patients. Cancer 2017;123:2860-66. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether clinical risk factors could further distinguish children with intermediate-risk Hodgkin lymphoma (HL) with rapid early and complete anatomic response (RER/CR) who benefit significantly from involved-field RT (IFRT) from those who do not, and thereby aid refinement of treatment selection.Methods and Materials: Children with intermediate-risk HL treated on the Children's Oncology Group AHOD 0031 trial who achieved RER/CR with 4 cycles of chemotherapy, and who were randomized to 21-Gy IFRT or no additional therapy (n=716) were the subject of this study. Recursive partitioning analysis was used to identify factors associated with clinically and statistically significant improvement in event-free survival (EFS) after randomization to IFRT. Bootstrap sampling was used to evaluate the robustness of the findings.Result: Although most RER/CR patients did not benefit significantly from IFRT, those with a combination of anemia and bulky limited-stage disease (n=190) had significantly better 4-year EFS with the addition of IFRT (89.3% vs 77.9% without IFRT; P=.019); this benefit was consistently reproduced in bootstrap analyses and after adjusting for other prognostic factors.Conclusion: Although most patients achieving RER/CR had favorable outcomes with 4 cycles of chemotherapy alone, those children with initial bulky stage I/II disease and anemia had significantly better EFS with the addition of IFRT as part of combined-modality therapy. Further work evaluating the interaction of clinical and biologic factors and imaging response is needed to further optimize and refine treatment selection. [ABSTRACT FROM AUTHOR]

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012).Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography-based volumetric RT planning on COG protocols AHOD0031 and AHOD0831.Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions.Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT. [ABSTRACT FROM AUTHOR]

Follicular lymphoma ( FL) in young adults ( YA, <40 years old) is uncommon, and the clinical characteristics and outcomes of this group are not well defined. We conducted a retrospective database review of 427 patients with newly diagnosed FL aged 65 years or less registered at Princess Margaret Cancer Centre between 1995 and 2010. YA ( n = 61) and those 40-65 ( n = 366) were compared with regards to clinical stage at diagnosis, FL International Prognostic Index ( FLIPI) score, and the following clinical outcomes: time to second treatment, cause-specific survival (CSS) and overall survival (OS). At diagnosis, stage and FLIPI score were similar, as were the proportion of patients requiring therapy ( YA 75% versus older adults 71%). Median follow-up was 8·1 years. Time to second therapy was similar in both age groups (5-year probability 23% YA versus 27% older adults; Gray's P-value = 0·76). Ten-year OS was significantly higher for YA (87% versus older adults 72%; P = 0·029). On multivariate analysis, age <40 years, low FLIPI score and observation as initial management were favourable prognostic factors for OS and CSS. We conclude that YA with FL have a favourable prognosis compared to older patients; whether this reflects competing mortality risks or age-related differences in lymphoma biology warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit. [ABSTRACT FROM AUTHOR]

BACKGROUND Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL. METHODS We evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy. RESULTS Median age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS Screening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations. Cancer 2014;120:2507-2513. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

Mantle-cell lymphoma (MCL) is a rare cancer, with the majority of patients (pts) presenting in stage Ill-IV and the outcomes are poor. To determine the curability of localized MCL, we examine stage I-II pts at our institution between 1990-2007.26 pts with stage I (38%) and stage II (62%) were referred. Sites involved were head and neck in 73%. Five had a blastoid variant. Five patients were treated with palliative intent. Analysis was focused on pts treated with a curative intent (21 pts): 17 CT-I- RT, 2 RT, 2 CT followed by ASCT. 13 patients received CHOP, 5-RCHOP, 1-CVP; most received ≤ 6 cycles.The RT median dose was 35Gy and IFRT for the majority. For 21 pts treated with a curative intent, median follow up was 5.8 years. The overall response rate was 95%. Among the 19 CR/CRu pts, 9 relapsed for a 5-year relapse rate of 46%. Relapses were mainly observed at distant sites, 3 were in GI tract, 1 had both local and distant relapse. Median PFS and OS were 3.2 and 6.4years, respectively. 5-year OS was 62%. In univariate analysis, blastoid variant and stage II were prognostic factors for PFS. Multivariate analysis could not be performed due to the small sample size. With a treatment approach using combined CT+RT for stage I-II MCL, local control was achieved in 94%. Systemic relapse remains a significant problem, especially for stage II and blastoid variant. Radiotherapy should remain part of curative treatment plan in stage I-II MCL. [ABSTRACT FROM AUTHOR]

We conducted a multi-institutional population-based analysis of the survival and toxicity associated with the addition of rituximab to chemotherapy for patients with diffuse large B-cell lymphoma ( DLBCL), including patients aged ≥80 years, who were excluded from published randomized trials. Using population-based registries in Ontario, we identified 4021 patients who received chemotherapy with or without rituximab (R- CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone] or CHOP) for DLBCL between 1996 and 2007, including 397 patients aged ≥80 years. After propensity score matching, the overall survival ( OS) and significant toxicities for R- CHOP and CHOP treatment groups were compared. R- CHOP was associated with a significant increase in 5-year OS compared to CHOP alone (62% vs. 54%; hazard of death = 0·78, P = 0·0004). Survival benefit was seen in all age groups, including those aged ≥80 years. Patients treated with rituximab did not have a significant increase in 1-year hospitalization rates for cardiac, pulmonary, gastrointestinal or neurological diagnoses compared to those treated with CHOP alone. The addition of rituximab to CHOP improves survival in the general population of patients with DLBCL and produces early survival benefit for very elderly patients, without any significant increase in the risk of serious toxicity. [ABSTRACT FROM AUTHOR]

Background: Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients. Methods: Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient. Results: The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62). Conclusions: The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Computed tomography (CT) and magnetic resonance imaging (MRI) utilization in Ontario increased drastically since the early 1990s. The effect of an increased number of cancer diagnoses, and an increase in indications for scans has not been assessed. This study was conducted to determine trends in utilization of CT and MRI in cancer patients in Ontario over a period of 9 years. Methods: Using Ontario Health Insurance Plan billing data linked to the Ontario Cancer Registry, rates of CT and MRI were analyzed by region, year, scan type and socioeconomic status. Results: CT in cancer patients increased 2.3-fold and accounted for approximately 24% of these scans. MRI in cancer patients increased by 4.2-fold and accounted for approximately 10% of these scans. Imaging rates for cancer patients increased more gradually than that of the general population. Substantial variation in the rate of both scans by region of patient residence existed. Even greater variation by the location of the scanner was demonstrated, indicating that many cancer patients traveled outside their region for imaging. There was little evidence of variation in scanning rates by socioeconomic status. Conclusion: A minority of CT and MRI performed in Ontario are for cancer care. Regional variation in imaging rates suggest that utilization guidelines be developed or knowledge transfer initiatives improve compliance to existing guidelines are needed. A significant number of cancer patients travel outside their region for diagnostic imaging; this should influence decisions about the location of new scanners. [Copyright &y& Elsevier]

Background: Partnership for Health-2 (PFH-2) is a web-based version of Partnership for Health, an evidence-based smoking cessation intervention for childhood cancer survivors. This paper describes the PFH-2 intervention and baseline data collection. Methods: 374 childhood and young adult cancer survivors were recruited from five cancer centers and participated in the baseline assessment. At baseline, participants completed measures of their smoking behavior, self-efficacy and stage of change for quitting smoking as well as psychological and environmental factors that could impact their smoking behavior. Results: At baseline, 93% of survivors smoked in the past seven days; however, 89% smoked a pack or less during this period. Forty-seven percent were nicotine dependent, and 55% had made at least one quit attempt in the previous year. Twenty-two percent of survivors were in contemplation for quitting smoking; of those 45% were somewhat or very confident that they could quit within six months. Sixty-three percent were in preparation for quitting smoking; however, they had relatively low levels of confidence that they could quit smoking in the next month. In multivariate analyses, stage of change, self-efficacy, social support for smoking cessation, smoking policy at work and home, fear of cancer recurrence, perceived vulnerability, depression, BMI, and contact with the healthcare system were associated with survivors' smoking behavior. Discussions/Conclusions: A large proportion of the sample was nicotine dependent, yet motivated to quit. Individual- interpersonal- and environmental-level factors were associated with survivors' smoking behavior. Smoking is particularly dangerous for childhood and young adult cancer survivors. This population may benefit from a smoking cessation intervention designed to build self-efficacy and address other known predictors of smoking behavior. [ABSTRACT FROM AUTHOR]

The case-cohort design is an economical solution to studying the association between an exposure and a rare disease. When the disease of interest has a delayed occurrence, then other types of event may preclude observation of the disease of interest giving rise to a competing risk situation. In this paper, we introduce a modification of the pseudolikelihood proposed by Prentice ( Biometrika 1986; 73:1-11) for the analysis of case-cohort design, to accommodate the existence of competing risks. The modification is based on the Fine and Gray ( J. Amer. Statist. Assoc. 1999; 94:496-509) approach to enable the modeling of the hazard of subdistribution. We show through simulations that the estimate that maximizes this modified pseudolikelihood is almost unbiased. The predictive probabilities based on the model are close to the theoretical probabilities. The variance for the estimates can be calculated using the jackknife approach. An application of this method on the analysis of late cardiac morbidity among Hodgkin Lymphoma survivors is presented. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study was conducted to evaluate the long-term outcomes in patients with stage IE and IIEmucosa-associated lymphoid tissue (MALT) lymphomas treated with involved field radiotherapy (RT). METHODS:Between 1989 and 2004, 192 patients with stage I and II MALT lymphomas were treated. The report focuses on 167patients who received RT. The median age of patients was 58 years with a female predominance (2:1). Presentingsites were as follows: orbital adnexa in 71 patients, salivary glands in 28 patients, stomach in 25 patients, thyroid in 21patients, and other sites in 22 patients. The median dose to nonorbital sites was 30 grays (Gy) (range, 17.5-35 Gy)and was 25 Gy for the orbit (range, 25-35 Gy). The median follow-up was 7.4 years (range, 0.67-16.20 years).RESULTS: Complete response and complete response, unconfirmed (CR/CRu) was noted in 166 (99%) patients. The10-year recurrence-free rate (RFR) was 76%, the disease-free survival (DFS) rate was 68%, the overall survival (OS)rate was 87%, and the cause-specific survival rate was 98%. According to presenting site, the 10-year RFR was 95%for thyroid, 92% for stomach, 68% for salivary glands, and 67% for orbit. Patients with thyroid and gastric MALTs hadbetter outcome compared with patients with MALTs diagnosed at other sites (P=.004). Among those patients whoachieved CR, 19% developed disease recurrence (n=31), chiefly in distant sites or untreated contralateral-pairedorgans. At the time of disease recurrence, 7 patients (23%) had transformed to diffuse large B-cell lymphoma, 2 ofwhom died of lymphoma. The 5-year OS rate after treatment failure was 83%. CONCLUSIONS: Patients with localized MALT lymphomas are reported to have excellent clinical outcome after moderate-dose RT, and some are likely cured.In the current study, thyroid and gastric MALTs were found to have significantly less risk of distant recurrence. Despite disease recurrence, the overall survival remains excellent in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Late complications (cardiac toxicities, secondary lung, and breast cancer) remain a significant concern in the radiation treatment of Hodgkin’s lymphoma (HL). To address this issue, predictive dose-risk models could potentially be used to estimate radiotherapy-related late toxicities. This study investigates the use of deformable image registration (DIR) and navigator channels (NCs) to reconstruct 3D lung models from 2D radiographic planning images, in order to retrospectively calculate the treatment dose exposure to HL patients treated with 2D planning, which are now experiencing late effects. Methods: Three-dimensional planning CT images of 52 current HL patients were acquired. 12 image sets were used to construct a male and a female population lung model. 23 “Reference” images were used to generate lung deformation adaptation templates, constructed by deforming the population model into each patient-specific lung geometry using a biomechanical-based DIR algorithm, MORFEUS. 17 “Test” patients were used to test the accuracy of the reconstruction technique by adapting existing templates using 2D digitally reconstructed radiographs. The adaptation process included three steps. First, a Reference patient was matched to a Test patient by thorax measurements. Second, four NCs (small regions of interest) were placed on the lung boundary to calculate 1D differences in lung edges. Third, the Reference lung model was adapted to the Test patient’s lung using the 1D edge differences. The Reference-adapted Test model was then compared to the 3D lung contours of the actual Test patient by computing their percentage volume overlap (POL) and Dice coefficient. Results: The average percentage overlapping volumes and Dice coefficient expressed as a percentage between the adapted and actual Test models were found to be 89.2±3.9% (Right lung=88.8%; Left lung=89.6%) and 89.3±2.7% (Right=88.5%; Left=90.2%), respectively. Paired T-tests demonstrated that the volumetric reconstruction method made a statistically significant improvement to the population lung model shape (p<0.05). The error in the results were also comparable to the volume overlap difference observed between inhale and exhale lung volumes during free-breathing respiratory motion (POL:p=0.43; Dice:p=0.20), which implies that the accuracies of the reconstruction method are within breathing constraints and would not be the confining factor in estimating normal tissue dose exposure. Conclusions: The result findings show that the DIR-NC technique can achieve a high degree of reconstruction accuracy, and could be useful in approximating 3D dosimetric representations of historical 2D treatment. In turn, this could provide a better understanding of the biophysical relationship between dose-volume exposure and late term radiotherapy effects. [ABSTRACT FROM AUTHOR]

Age- and sex-specific estimates of the rate of cardiac morbidity among Hodgkin lymphoma (HL) patients treated with doxorubicin-based chemotherapy and radiation therapy (RT) are scarce. We evaluated the risk of hospital admission for cardiac disease in 615 HL patients, adjusting for age, sex, treatment, cardiac risk factors and competing causes of death. Compared with the general population, the risk of cardiac morbidity was highest among patients treated with both doxorubicin and mediastinal RT (HR = 2.77, p < 0.0001). Mediastinal RT without chemotherapy also significantly increased the risk (HR = 1.82, p = 0.038). For females and males treated with doxorubicin plus mediastinal RT at age 40, the estimated 15-year incidence rate of cardiac hospitalisation were 7.3% and 16.5%, respectively, rates 5-15% higher than expected. These results suggest that the risk of clinically important cardiac toxicity following HL treatment that includes both doxorubicin and mediastinal RT may be greater than that reported in prior studies of patients treated with RT alone. [ABSTRACT FROM AUTHOR]

Background: Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Methods: Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organspecific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Results: Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. Conclusion: The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the incidence of radiation pneumonitis (RP) in a modern Hodgkin’s lymphoma (HL) cohort, and to identify any clinically relevant parameters that may influence the risk of RP. Methods and Materials: Between January 2003 and February 2005, 64 consecutive HL patients aged 18 years or older receiving radical mediastinal radiation therapy (RT) were retrospectively reviewed. Symptomatic cases of radiation pneumonitis were identified. Dose–volume histogram parameters, including V13, V20, V30, and mean lung dose (MLD), were quantified. Results: At a median follow-up of 2.1 years, the actuarial survival for all patients was 91% at 3 years. There were 2 (2/64) cases of Radiation Therapy Oncology Group (RTOG) Grade 2 RP (incidence 3.1%). Both index cases with corresponding V20 values of 47.0% and 40.7% were located in the upper quartile (2/16 cases), defined by a V20 value of ≥36%, an incidence of 12.5% (p = 0.03). Similarly for total MLD, both index cases with values of 17.6 Gy and 16.4 Gy, respectively, were located in the upper quartile defined by MLD ≥14.2 Gy, an incidence of 11.8% (2/17 cases, p = 0.02). Conclusions: Despite relatively high V20 values in this study of HL patients, the incidence of RP was only 3%, lower compared with the lung cancer literature. We suggest the following clinically relevant parameters be considered in treatment plan assessment: a V20 greater than 36% and an MLD greater than 14 Gy, over and above which the risk of RTOG Grade 2 or greater RP would be considered clinically significant. [Copyright &y& Elsevier]

Treatments for Hodgkin lymphoma are associated with large relative risks of acute myeloid leukemia (AML), but there are few estimates of the excess absolute risk (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N = 35511) were identified within 14 population-based cancer registries in Nordic countries and North America from January 1, 1970, through December 31, 2001. We used Poisson regression analysis to model the EAR of AML, per 10000 person-years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8 expected, unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess absolute risk for AML was highest during the first 10 years after Hodgkin lymphoma diagnosis but remained elevated thereafter. In subsequent analyses, adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year interval, the EAR was statistically significantly (P<.001) larger in patients diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed before 35 years of age. The EAR of AML declined statistically significantly after 1984 (7.0 to 4.2 and 16.4 to 9.9 in the <35 and ≥35 age groups, respectively), which may be associated with modifications in chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To examine error rates in the delivery of radiation therapy (RT), technical factors associated with RT errors, and the influence of a quality improvement intervention on the RT error rate. Methods and materials: We undertook a review of all RT errors that occurred at the Princess Margaret Hospital (Toronto) from January 1, 1997, to December 31, 2002. Errors were identified according to incident report forms that were completed at the time the error occurred. Error rates were calculated per patient, per treated volume (≥1 volume per patient), and per fraction delivered. The association between tumor site and error was analyzed. Logistic regression was used to examine the association between technical factors and the risk of error. Results: Over the study interval, there were 555 errors among 28,136 patient treatments delivered (error rate per patient = 1.97%, 95% confidence interval [CI], 1.81–2.14%) and among 43,302 treated volumes (error rate per volume = 1.28%, 95% CI, 1.18–1.39%). The proportion of fractions with errors from July 1, 2000, to December 31, 2002, was 0.29% (95% CI, 0.27–0.32%). Patients with sarcoma or head-and-neck tumors experienced error rates significantly higher than average (5.54% and 4.58%, respectively); however, when the number of treated volumes was taken into account, the head-and-neck error rate was no longer higher than average (1.43%). The use of accessories was associated with an increased risk of error, and internal wedges were more likely to be associated with an error than external wedges (relative risk = 2.04; 95% CI, 1.11–3.77%). Eighty-seven errors (15.6%) were directly attributed to incorrect programming of the “record and verify” system. Changes to planning and treatment processes aimed at reducing errors within the head-and-neck site group produced a substantial reduction in the error rate. Conclusions: Errors in the delivery of RT are uncommon and usually of little clinical significance. Patient subgroups and technical factors associated with errors can be identified. The introduction of new technology can produce new ways for errors to occur, necessitating ongoing evaluation of RT errors for quality assurance. Modifications to processes of care can produce important reductions in error rates. [Copyright &y& Elsevier]

Purpose: Understanding the relationship between normal tissue dose and delayed radiation toxicity is an important component of developing more effective radiation therapy. Late outcome data are generally available only for patients who have undergone 2-dimensional (2D) treatment plans. The purpose of this study was to evaluate the accuracy of 3D normal tissue dosimetry derived from reconstructed 2D treatment plans in Hodgkin''s lymphoma (HL) patients. Methods and Materials: Three-dimensional lung, heart, and breast volumes were reconstructed from 2D planning radiographs for HL patients who received mediastinal radiation therapy. For each organ, a reference 3D organ was modified with patient-specific structural information, using deformable image processing software. Radiation therapy plans were reconstructed by applying treatment parameters obtained from patient records to the reconstructed 3D volumes. For each reconstructed organ mean dose (Dmean) and volumes covered by at least 5 Gy (V5) and 20Gy (V20) were calculated. This process was performed for 15 patients who had both 2D and 3D planning data available to compare the reconstructed normal tissue doses with those derived from the primary CT planning data and also for 10 historically treated patients with only 2D imaging available. Results: For patients with 3D planning data, the normal tissue doses could be reconstructed accurately using 2D planning data. Median differences in Dmean between reconstructed and actual plans were 0.18 Gy (lungs), −0.15 Gy (heart), and 0.30 Gy (breasts). Median difference in V5 and V20 were less than 2% for each organ. Reconstructed 3D dosimetry was substantially higher in historical mantle-field treatments than contemporary involved-field mediastinal treatments: average Dmean values were 15.2 Gy vs 10.6 Gy (lungs), 27.0 Gy vs 14.3 Gy (heart), and 8.0 Gy vs 3.2 Gy (breasts). Conclusions: Three-dimensional reconstruction of absorbed dose to organs at risk can be estimated accurately many years after exposure by using limited 2D data. Compared to contemporary involved-field treatments, normal tissue doses were significantly higher in historical mantle-field treatments. These methods build capacity to quantify the relationship between 3D normal tissue dose and observed late effects. [Copyright &y& Elsevier]