Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms

SUMMARY OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy. RESULTS: With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively. CONCLUSION: The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

Clinical study of total marrow and lymphatic irradiation in children using helical tomotherapy / 中华放射肿瘤学杂志

Objective To evaluate the feasibility of total marrow and lymphatic irradiation (TMLI)with helical tomotherapy as a conditioning regimen before hematopoietic stem cell transplantation (HSCT).Methods Seven children with acute lymphoblastic leukemia and aplastic anemia were recruited as study subjects.The median age was 7 years old.The prescribed dose was 12 Gy/6 fractions twice daily.The exposure dose of the target and the organs at risk between helical helical tomotherapy-based TMLI regimen and total body irradiation (TBI) regimen were statistically compared,and acute toxicity grading was performed for all patients.Results Compared with the TBI regimen,the average exposure dose reduction for organs at risk after the TMLI regimen was ranged from 4.2％ to 40.6％.The average exposure dose reduction for the kidney was the largest among all organs.The acute toxicities experienced by all patients were graded and recorded including 2 cases of nausea,5 cases of vomiting,1 case of anorexia,1 case of eryhema,3 cases of diarrhea,and 1 case of oral mucositis.Only grade 1-2 toxicities were observed,and no grade 3-4 toxicities occurred.Conclusions The findings in this study confirm the feasibility of helical helical tomotherapy-based TMLI regimen.Compared with the TBI regimen,the mean duration of treatment for the TMLI regimen with an equivalent dose is not increased.The exposure dose experienced by organs at risk is reduced and the predicted incidence rate is decreased when the TMLI regimen is employed,which provides a myeloablative pretreatment strategy.However,the long-term toxicity of TMLI regime remains to be evaluated by clinical trials.

Patterns of initial failure after resection for gallbladder cancer: implications for adjuvant radiotherapy

PURPOSE: This study sought to identify potential candidates for adjuvant radiotherapy and patterns of regional failure in patients who underwent curative-intent surgery for gallbladder cancer. MATERIALS AND METHODS: Records for 70 patients with gallbladder cancer who underwent curative resection at a single institution between 2000 and 2016 were analysed retrospectively. No patients received adjuvant radiotherapy. Initial patterns of failure were evaluated. Regional recurrence was categorized according to the definitions of lymph node stations suggested by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. RESULTS: Median follow-up was 23 months. Locoregional recurrence as any component of first failure occurred in 29 patients (41.4%), with isolated locoregional recurrence in 13 (18.6%). Regional recurrence occurred in 23 patients, and 77 regional recurrences were identified. Commonly involved regional stations were #13, #12a2, #12p2, #12b2, #16a2, #16b1, #9, and #8. Independent prognostic factors for locoregional recurrence were ≥pT2 disease (hazard ratio [HR], 5.510; 95% confidence interval [CI], 1.260–24.094; p = 0.023) and R1 resection (HR, 6.981; 95% CI, 2.378–20.491; p < 0.001). CONCLUSION: Patients with pT2 disease or R1 resection after curative surgery for gallbladder cancer may benefit from adjuvant radiotherapy. Our findings on regional recurrence may help physicians construct a target volume for adjuvant radiotherapy.

Prognostic Impact of Elective Supraclavicular Nodal Irradiation for Patients with N1 Breast Cancer after Lumpectomy and Anthracycline Plus Taxane-Based Chemotherapy (KROG 1418): A Multicenter Case-Controlled Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. MATERIALS AND METHODS: We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. RESULTS: A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. CONCLUSION: We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

Incidental irradiation of internal mammary lymph nodes in breast cancer: conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy / Irradiação incidental da cadeia mamária interna no câncer de mama: comparação entre a técnica convencional (bidimensional) e a técnica tridimensional

Abstract Objective: To evaluate incidental irradiation of the internal mammary lymph nodes (IMLNs) through opposed tangential fields with conventional two-dimensional (2D) or three-dimensional (3D) radiotherapy techniques and to compare the results between the two techniques. Materials and Methods: This was a retrospective study of 80 breast cancer patients in whom radiotherapy of the IMLNs was not indicated: 40 underwent 2D radiotherapy with computed tomography for dosimetric control, and 40 underwent 3D radiotherapy. The total prescribed dose was 50.0 Gy or 50.4 Gy (2.0 or 1.8 Gy/day, respectively). We reviewed all plans and defined the IMLNs following the Radiation Therapy Oncology Group recommendations. For the IMLNs, we analyzed the proportion of the volume that received 45 Gy, the proportion of the volume that received 25 Gy, the dose to 95% of the volume, the dose to 50% of the volume, the mean dose, the minimum dose (Dmin), and the maximum dose (Dmax). Results: Left-sided treatments predominated in the 3D cohort. There were no differences between the 2D and 3D cohorts regarding tumor stage, type of surgery (mastectomy, breast-conserving surgery, or mastectomy with immediate reconstruction), or mean delineated IMLN volume (6.8 vs. 5.9 mL; p = 0.411). Except for the Dmin, all dosimetric parameters presented higher mean values in the 3D cohort (p < 0.05). The median Dmax in the 3D cohort was 50.34 Gy. However, the mean dose to the IMLNs was 7.93 Gy in the 2D cohort, compared with 20.64 Gy in the 3D cohort. Conclusion: Neither technique delivered enough doses to the IMLNs to achieve subclinical disease control. However, all of the dosimetric parameters were significantly higher for the 3D technique.

Resumo Objetivo: Avaliar a irradiação incidental dos linfonodos da cadeia mamária interna (LCMIs) com campos tangenciais opostos por meio de radioterapia bidimensional (2D) convencional ou tridimensional (3D) e comparar as duas técnicas quanto aos resultados obtidos. Materiais e Métodos: Trata-se de um estudo retrospectivo com 80 pacientes com câncer de mama sem indicação de radioterapia dos LCMIs: 40 foram submetidos a radioterapia 2D com tomografia computadorizada para controle dosimétrico e 40 foram submetidos a radioterapia 3D. A dose total prescrita foi 50,0 Gy ou 50,4 Gy (2,0 ou 1,8 Gy/dia, respectivamente). Os planos de tratamento foram analisados e os LCMIs foram definidos conforme as recomendações do Radiation Therapy Oncology Group. No tocante aos LCMIs, foram analisadas a proporção do volume que recebeu 45 Gy, a proporção do volume que recebeu 25 Gy, a dose para 95% do volume, a dose para 50% do volume, a dose média, a dose mínima (Dmín) e a dose máxima (Dmáx). Resultados: Tratamentos do lado esquerdo predominaram na coorte 3D. Não houve diferenças entre as coortes 2D e 3D quanto ao estágio do tumor, ao tipo de cirurgia (mastectomia, cirurgia conservadora ou mastectomia com reconstrução imediata) ou à média do volume delineado dos LCMIs (6,8 vs. 5,9 mL; p = 0,411). À exceção da Dmín, todos os parâmetros dosimétricos apresentaram médias maiores na coorte 3D (p < 0,05). A mediana da Dmáx na coorte 3D foi 50,34 Gy. No entanto, a dose média nos LCMIs foi 7,93 Gy na coorte 2D e 20,64 Gy na coorte 3D. Conclusão: Nenhuma das duas técnicas emitiu doses suficientes aos LCMIs para que se alcançasse o controle subclínico da doença. No entanto, todos os parâmetros dosimétricos foram significativamente maiores com a técnica 3D.

Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

PURPOSE: To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4-72 Gy (39.6-45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. RESULTS: The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. CONCLUSION: No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC.

Radiation Pneumonitis in Association with Internal Mammary Node Irradiation in Breast Cancer Patients: An Ancillary Result from the KROG 08-06 Study / 한국유방암학회지

PURPOSE: The aim of this study is to present the incidence of radiation pneumonitis (RP) reported within 6 months after treatment for breast cancer with or without internal mammary node irradiation (IMNI). METHODS: In the Korean Radiation Oncology Group (KROG) 08-06 phase III randomized trial, patients who were node-positive after surgery were randomly assigned to receive radiotherapy either with or without IMNI. A total of 747 patients were enrolled, and three-dimensional treatment planning with computed tomography simulation was performed for all patients. Of the 747 patients, 722 underwent chest X-rays before and within 6 months after radiotherapy. These 722 patients underwent evaluation, and RP was diagnosed on the basis of chest radiography findings and clinical symptoms. The relationship between the incidence of RP and clinical/dosimetric parameters was analyzed. RESULTS: RP developed in 35 patients (4.8%), including grade 1 RP in 26 patients (3.6%), grade 2 RP in nine patients (1.2%); there was no incidence of grade 3 or higher RP. Grade 2 RP cases were observed in only the IMNI group. The risk of developing RP was influenced by IMNI treatment; pneumonitis occurred in 6.5% of patients (n=23/356) who underwent IMNI and in 3.3% of patients (n=12/366) who did not (p=0.047). The differences in lung dosimetric parameters (mean lung dose, V10–40) were statistically significant between the two groups. CONCLUSION: IMNI treatment resulted in increased radiation exposure to the lung and a higher rate of RP, but the incidence and severity of RP was minimal and acceptable. This minor impact on morbidity should be balanced with the impact on survival outcome in future analyses.

Research progress of lymph node metastasis in esophageal cancer / 国际肿瘤学杂志

Lymph nodes (LN)are the main parts of the esophageal cancer metastasis,and the current status of LN is the important indicator of prognosis.LN metastasis appears in early stage of esophageal cancer.One side,LN metastasis easily appears in the regions near the tumor and some special areas.On the other side,LN metastasis has the characteristics of wide metastasis and skip metastasis.Therefore,the researches of the pattern of esophageal cancer lymph node metastasis can help to comform the scope of the esophageal cancer lymph node dissection and the target regions of radiotherapy.

Radiation Treatment in Pathologic N0-N1 Patients Treated with Neoadjuvant Chemotherapy Followed by Surgery for Locally Advanced Breast Cancer / 한국유방암학회지

PURPOSE: This study evaluated the treatment results and the necessity to irradiate the supraclavicular lymph node (SCN) region in pathological N0-N1 (pN0-N1) patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery and radiotherapy (RT). METHODS: Between 1996 and 2008, 184 patients with initial tumor size >5 cm or clinically positive lymph nodes were treated with NAC followed by surgery and RT. Among these patients, we retrospectively reviewed 98 patients with pN0-N1. Mastectomy was performed in 55%. The pathological lymph node stage was N0 in 49% and N1 in 51%. All patients received adjuvant RT to chest wall or breast and 56 patients (57%) also received RT to the SCN region (SCNRT). RESULTS: At 5 years, locoregional recurrence (LRR)-free survival, distant metastasis-free survival, disease-free survival (DFS), and overall survival rates were 93%, 83%, 81%, and 91%, respectively. In pN0 patients, LRR was 7% in SCNRT- group and 5% in SCNRT+ group. In pN1 patients, LRR was 7% in SCNRT- group and 6% in SCNRT+ group. There was no significant difference of LRR, regardless of SCNRT. However, in pN1 patients, there were more patients with poor prognostic factors in the SCNRT+ group compared to SCNRT- group. These factors might be associated with worse DFS in the SCNRT+ group, even though RT was administered to the SCN region. CONCLUSION: Our study showed the similar LRR, regardless of SCNRT in pN0-pN1 breast cancer patients after NAC followed by surgery. Prospective randomized trial is called for to validate the role of SCNRT.

Radiation Pneumonitis in Breast Cancer Patients Who Received Radiotherapy Using the Partially Wide Tangent Technique after Breast Conserving Surgery / 한국유방암학회지

PURPOSE: We assessed the risk of radiation pneumonitis (RP) in terms of dosimetric parameters in breast cancer patients, who received radiotherapy using the partially wide tangent technique (PWT), following breast conservation surgery (BCS). METHODS: We analyzed the data from 100 breast cancer patients who underwent radiotherapy using PWT. The entire breast, supraclavicular lymph node, and internal mammary lymph node (IMN) were irradiated with 50.4 Gy in 28 fractions. RP was scored on a scale of 0 to 5, based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The dosimetric parameters, used in analysis for the ipsilateral lung, were the mean lung dose (MLD), V5 (percentage of lung volume that received a dose of 5 Gy or more)-V50, and normal tissue complication probability (NTCP). RESULTS: Of the 100 patients, three suffered from symptomatic RP (symptom grade > or =2), but were relieved by supportive care. The risk of RP was not correlated with the treatment regimen. RP associated mostly with asymptomatic minimal pulmonary radiologic change or mild dry cough developed more frequently in the group with MLD > or =20.5 Gy or NTCP > or =23% than in the group with MLD <20.5 Gy and NTCP <23% (48.6% vs. 25.4%, p=0.018). CONCLUSION: Dosimetric parameters of MLD and NTCP were correlated with the incidence of RP, but the clinical impact was minimal. We suggest that PWT is a safe technique for the treatment of IMN for BCS patients with low risk of symptomatic RP.

A dosimetric comparison of three plans in simultaneous integrated boost intensity-modulated radiotherapy in cervical esophageal carcinoma undergoing prophylactic lymphatic irradiation / 中华放射医学与防护杂志

Objective To evaluate the optimized simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) plans in cervical esophageal carcinoma underwent prophylactic lymphatic irradiation.MethodsSix patients with cervical esophageal carcinoma were studied.The gross tumor volume (GTV) and clinical target volume (CTV) (including bilateral mid-lower neck and supraclavicular lymph drainage regions,upper mediastinal lymph drainage regions) were delineated on sim-CT images,GTV and CTV were uniformly expanded by 5 mm to create PGTV and PTV.Five fields(5F) ,7F and 9F SIB-IMRT plans were designed.The prescribed doses to PGTV and PTV were 66 Gy and 60 Gy in 30 fractions respectively.The parameters of dose-volume histograms in three groups planning were compared.Results The values of conformity index(CI) of PGTV were 0.56,0.62 and 0.69 (F =6.22,P ＜0.01 ),the V66 with 88.24% ,95.03% and 94.91% ( F = 4.39,P ＜ 0.05 ) and D95 with 6539.67,6601.83 and 6602.00 cGy (F=4.46,P ＜0.05) in 5F,7F and 9F SIB-IMRT plans.The values of CI,V66 and D95 of PTV were 0.80,0.85 and 0.87 (F=11.29,P＜0.01),with 91.64%,94.05% and 95.06% (F=4.10,P＜0.05) and with 5934.00,5987.17 and 6006.33 cGy (F =4.01,P ＜0.05).The values of maximal dose of spinal cord were 4707.17,4497.83 and 4357.00 cGy( F = 11.26 ,P ＜0.011 ) in 5F ,7F and 9F SIB-IMRT plans.The values of all dosimetic parameters about PGTV and PTV were same in 7F and 9F SIB-IMRT plans ( all P ＞ 0.05 ).Conclusion 7F-SIB-IMRT plan is best one scheme for cervical esophageal carcinoma underwent prophylactic lymphatic irradiation.

Primed total lymphoid irradiation of the recipient in living donor kidney graft / 解放军医学杂志

Objective To investigate the safety and effectiveness of the application of an immunosuppressing primed total lymphoid irradiation (TLI) of the recipient in kidney transplantation of living donor kidney graft. Methods 5 recipients, 3 males and 2 females with the average age of 27, underwent the primed regimen of TLI. As to 6 HLA-A, B, DR antigens of donors and recipients, 4 HLA antigen mismatches were found in one case, 3 mismatches in two cases, and 1 mismatch in two cases. The donor grafts were procured by the technique of hand-assisted transperitoneal laparoscopic living donor nephrectomy (HLDN). The primed regimen of TLI was carried out 5 days before the operation in a dosage 90 cGy/d. The intra- and postoperative immunosuppressant protocols for these cases were similar to that for the other cases, but the doses were reduced slightly. WBC, total T cell, CD4~+ and CD8~+ T cell subsets and Th1/Th2 immune deviation were examined in recipients periodically. The function of the grafted kidney, acute rejection frequency, and side effects of TLI were also observed. Results In the recipients undergone TLI, the total WBC and T cell, CD4~+ and CD8~+ subsets were reduced to a base value at 1-2 weeks post-transplantation and did not restore to the pre-transplantation levels until the investigation was ended. A particular phenomenon showing that in TLI based regimen T cells were shifted from Th1 to Th2 cells was observed. No side effects of TLI, such as infection, were found during the observation. Transplanted kidneys functioned normally and no rejection episodes were observed up to the end of the study. The immunosuppressant doses for those 5 cases were lower than that of conventional protocol. Conclusions TLI based non-myeloablative primed regimen is a safe and effective method for immunosuppression without serious side effects, and it can markedly alleviate kidney transplant rejection and reduce the dosage of immunosuppressive drugs.

Clinical study of infusion of peripheral blood stem cells of the donor to renal transplantation recipient / 解放军医学杂志

Objective To study the chimerism formation in kidney transplantation recipient receiving peripheral blood stem cells (PBSCs) of the donor after the patient received preoperative total lymphoid irradiation (TLI). Methods 5 patients of living donor kidney transplantation were involved in present study. The mean age of donors was 40 and that of recipients was 27. There was one patients with 4 HLA antigen mismatches out of 6 HLA-A, B, DR antigens, two patients with 3 HLA-mismatches, and two patients with 1 HLA-mismatch. The patients received TLI in doses 90cGy/d from day -5 to day -1. The immunosuppression protocol for these patients during operation and afteroperation was similar to that for other cases, but the dosage was slightly reduced. Donor PBSCs were harvested twice via leukapheresis after the administration of human recombinant granulocyte colony stimulating factor (G-CSF). PBSCs were infused intravenously to the recipients on postoperative day 4 and 7. Chimerism of peripheral blood cell in recipients was detected by PCR-SSP assays. The grafted kidney function, acute rejection frequency and GVHD episodes were also observed. Results After 5 days of G-CSF based mobilizing regimen, the average number of PBSCs harvested from donors was 34?10~6. At 1 month post-transplantation, donor type HLA-DR gene was detected in all the recipients. At 2 and 3 months post-transplantation, chimerism was not detectable in the recipient with 4 HLA antigens (including 2 HLA-DR) mismatched donor kidney and in the recipient with 3 HLA (including 2 HLA-DR and 1 HLA-B) mismatched donor, respectively. In the other 3 recipients, chimerism was still positive 3 months post-transplantation. There were no symptoms of GVHD or infections after infusion of PBSCs. Transplanted kidneys functioned normally and no rejection episodes were observed till the end of the study. The immunosuppressant dosage was lower for these 5 cases than those after conventional cadavar renal transplantation. Conclusions Non-myeloablative TLI conditioning regimen is a safe and effective method which can promote the engraftment of donor PBSCs and induce hemopoietic chimerism. Chimerism can alleviate rejection of the transplanted kidney and reduce the immunosuppressant dosage. Collection and infusion of PBSCs are simple, convenient, effective, and inexpensive, and it is an optimal source of hemopoietic stem cells.