Eastern Europe is represented by 22 countries of significant variability in population density and degree of economic development. They have been affected by past geopolitical isolation due to their ...association with the “Soviet Block.” Currently, all Eastern European countries except Slovenia are low- or middle-income level and 10 of them are part of European Union. Health care systems in Central and Eastern Europe have been influenced by the legacy of centralized soviet-era governance; however, most countries, particularly in European Union zone, have gone through health care reforms directed toward modernizing infrastructure and staffing. The level of health financing available through health insurance has increased in the region, although still lags behind the Western European levels. After adjusting for differing population age structures, overall incidence rates in both sexes are lower in Eastern and Central Europe compared with the Northern and Western European countries; however, mortality remains higher. There is an ongoing shortage of oncology services in Eastern Europe, including radiotherapy equipment and personnel. Eastern European radiotherapy field is highly diverse with large differences among countries regarding staffing structure, training, accreditation, and defined roles and responsibilities. The rapid diffusion of technological innovations has been identified as one of the most important factors driving the escalating health care expenses, and the need for better cost-effective solutions applicable to the local health care systems and levels of economic development.
Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid ...critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury.
Twenty-seven physicians, physicists, and researchers from 17 institutions with expertise met to discuss this issue. The definition of brainstem injury, imaging of this entity, clinical experience with photons and photons, and potential biological differences among these radiation modalities were thoroughly discussed and reviewed. The 3 largest US pediatric proton therapy centers collectively summarized the incidence of symptomatic brainstem injury and physics details (planning, dosimetry, delivery) for 671 children with focal posterior fossa tumors treated with protons from 2006 to 2016.
The average rate of symptomatic brainstem toxicity from the 3 largest US pediatric proton centers was 2.38%. The actuarial rate of grade ≥2 brainstem toxicity was successfully reduced from 12.7% to 0% at 1 center after adopting modified radiation guidelines. Guidelines for treatment planning and current consensus brainstem constraints for proton therapy are presented. The current knowledge regarding linear energy transfer (LET) and its relationship to relative biological effectiveness (RBE) are defined. We review the current state of LET-based planning.
Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.
Acute lymphoblastic leukemia Chang, John Han‐Chih; Poppe, Matthew M.; Hua, Chia‐Ho ...
Pediatric blood & cancer,
20/May , Letnik:
68, Številka:
S2
Journal Article
Recenzirano
Odprti dostop
The survival of patients with acute lymphoblastic leukemia (ALL) has improved significantly with the use of intensive multimodality treatment regimens including chemotherapy, high‐dose chemotherapy ...and stem cell rescue, and radiation therapy when indicated. This report summarizes the treatment strategies, especially radiation therapy in the Children's Oncology Group for children with ALL. Currently, radiation therapy is only indicated for children with high‐risk CNS involvement at diagnosis or relapse, testicular relapse and as part of the conditioning regimen for hematopoietic stem cell transplantation. Future research strategies regarding the indications for and dosages of radiation therapy and novel radiation techniques are discussed.
Total body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia. The most common ...adverse effect is pulmonary toxicity including idiopathic pneumonia syndrome (IPS). As centers adopt more advanced treatment planning techniques for TBI, total marrow irradiation (TMI), or total marrow and lymphoid irradiation (TMLI) there is a greater need to understand treatment-related risks for IPS for patients treated with conventional TBI. However, definitions of IPS as well as risk factors for IPS remain poorly characterized. In this study, we perform a critical review to further evaluate the literature describing pulmonary outcomes after TBI.
A search of publications from 1960-2020 was undertaken in PubMed, Embase, and Cochrane Library. Search terms included "total body irradiation", "whole body radiation", "radiation pneumonias", "interstitial pneumonia", and "bone marrow transplantation". Demographic and treatment-related data was abstracted and evidence quality supporting risk factors for pulmonary toxicity was evaluated.
Of an initial 119,686 publications, 118 met inclusion criteria. Forty-six (39%) studies included a definition for pulmonary toxicity. A grading scale was provided in 20 studies (17%). In 42% of studies the lungs were shielded to a set mean dose of 800cGy. Fourteen (12%) reported toxicity outcomes by patient age. Reported pulmonary toxicity ranged from 0-71% of patients treated with TBI, and IPS ranged from 1-60%. The most common risk factors for IPS were receipt of a TBI containing regimen, increasing dose rate, and lack of pulmonary shielding. Four studies found an increasing risk of pulmonary toxicity with increasing age.
Definitions of IPS as well as demographic and treatment-related risk factors remain poorly characterized in the literature. We recommend routine adoption of the diagnostic workup and the definition of IPS proposed by the American Thoracic Society. Additional study is required to determine differences in clinical and treatment-related risk between pediatric and adult patients. Further study using 3D treatment planning is warranted to enhance dosimetric precision and correlation of dose volume histograms with toxicities.
Although radiation therapy (RT) has been recognized for contributing to cardiovascular disease (CVD), it is unknown whether specific doses received by cardiovascular tissues influence development.
In ...this pilot study, we examined the contribution of RT dose distribution on the development of CVD events in patients with cancer within 5 years of RT.
A retrospective case-controlled design was used matching 28 cases receiving thoracic RT who subsequently developed an adverse CVD event with 28 controls based upon age, gender, and cancer type. Dose volume histograms of nongated computed tomography scans received during RT characterized the dose delivered to the heart. Heart chambers were segmented using an atlas approach, and radiomics features for the segmentation as well as planning dose in each chamber were tabulated for analysis.
No significant differences were observed in the RT dose statistics between groups, preexisting CVD, nor significant differences of RT doses delivered to distinct chambers of the heart. Cases were found to have greater CVD risk factors at the time of cancer diagnosis. Morphological significant differences for perimeter on border ( P = .043), equivalent spherical radius ( P = .050), and elongation ( P = .038) were observed, with preexisting CVD having the highest values (ie, larger hearts).
Traditional CVD risk factors were more prevalent in the cases who developed CVD. No differences were observed in doses of RT. Of note, we observed significant differences in heart morphology and mass in known diseased hearts on the pretreatment scans. These new metrics may have implications for the measurement and quantification of CVD.
This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), ...followed by allogeneic hematopoietic stem cell transplantation (HSCT).
The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period.
PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS.
A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.
The role of consolidative radiation therapy (RT) after complete response (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for stage III-IV diffuse ...large B-cell lymphoma (DLBCL) patients is unclear. We aimed to evaluate our institutional experience when consolidative RT is delivered to initial presenting sites or bulky sites in these patients.
We identified 211 histologically confirmed stage III-IV DLBCL patients who received R-CHOP from January 2000 to May 2012 at our institution. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using the log-rank test. Multivariate analyses were also performed using Cox proportional hazards model.
Detailed treatment records were available for 163 patients. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT. After median follow-up of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.7% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%), DC (92.9% vs 71.9%), PFS (85.1% vs 44.2%), and OS (92.3% vs 68.5%; all Ps<.0001) at 5 years compared with patients with R-CHOP alone. On multivariate analysis, consolidative RT and nonbulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Consolidative RT was also associated with marginal improved OS.
Forty-four percent of patients with advanced stage DLBCL failed at initial presenting sites after achieving CR to R-CHOP. Incorporation of consolidative RT as part of upfront treatment in these patients was associated with improved LC, PFS, and a trend towards improved OS.
Local recurrence has been demonstrated in previous studies to be one of the obstacles to cure in neuroblastoma. Radiation therapy indications, optimal dose, and technique are still evolving. Here we ...report our experience of high-risk neuroblastoma patients who received local radiation therapy as part of their cancer management.
We conducted a retrospective study of 34 high-risk neuroblastoma patients who received radiation therapy to local sites of disease from March 2001 until February 2007 at our institution as part of their multimodality therapy.
At a median follow-up of 33.6 months, 6 patients died of disease, 7 patients were alive with disease, and 21 patients were in clinical remission. Eleven patients relapsed, all distantly. Two patients failed locally in addition to distant sites. Both of these patients had persistent gross disease after induction chemotherapy and surgery. Our 3-year local control, event-free survival, overall survival were 94%, 66%, and 86%, respectively.
Patients with high-risk neuroblastoma in our series achieved excellent local control. Doses of 21-24 Gy to the primary tumor site appear to be adequate for local control for patients in the setting of minimal residual disease after induction chemotherapy and surgery. Patients with significant residual disease may benefit from radiation dose escalation, and this should be evaluated in a prospective clinical trial.
To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single ...institution.
We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014.
At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse-free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse-free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly.
Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.
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