Predictors of lymphopenia in esophageal cancer patients receiving photon or proton radiation therapy: A dosimetric analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 147-147 ◽  
Author(s):  
David M. Routman ◽  
Thomas J Whitaker ◽  
Courtney N. Day ◽  
William S. Harmsen ◽  
Michelle A. Neben-Wittich ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Lymphocyte Count ◽  
Organs At Risk ◽  
Absolute Lymphocyte Count ◽  
Continuous Variable ◽  
Oncologic Outcomes ◽  
Proton Radiation ◽  
Curative Intent

147 Background: Lymphopenia during radiation therapy (RT) has been associated with worse oncologic outcomes in a number of malignancies, including esophageal cancer (EC). No studies to date have investigated specific dosimetric parameters associated with this lymphopenia in EC. We performed an analysis of RT dose to multiple organs at risk (OARs) to investigate associations with grade 4 lymphopenia (G4L). Methods: Consecutive EC patients receiving curative intent chemoradiotherapy +/- surgery between July of 2015 and December of 2017 were included. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count <200/mm3. Dose to OARs including aorta, body, bone marrow, heart, liver, lung, and spleen were calculated. Univariate logistic regression analyses were performed for each OAR at the 1, 5, 10, 15, 20, 30, 35, 40, and 50 Gy levels with volume receiving dose ‘x’(VxGy) analyzed as a continuous variable per 10% increase. Clinical tumor volume (CTV) and RT modality (photon vs. proton) as well clinical factors including sex, stage (I/II vs. III/IV), age (per 10 year increase), and BMI (per 5 unit increase) were also analyzed. Results: One hundred forty-four pts were identified for inclusion. Seventy-nine pts received photon RT and 65 proton RT. Chemotherapy was weekly carbotaxol (99%). G4L at nadir was 40% overall (56% photon, 22% proton). By organ, body V1-V30Gy (OR 1.45-8.18, p<0.01), heart V1-V30Gy (OR 1.24-1.49, p<0.01), liver V1-V35Gy (OR 1.23-2.75, p<0.01), lung V1-V30Gy (OR 1.26-5.73 p<0.01), and spleen V1-V40Gy (OR 1.26-1.49 p<0.01) were highly associated with G4L whereas dose to aorta and bone marrow were not. Advanced stage (OR, 3.92 p<0.01), photon vs. proton (OR 4.58 p<0.01), and CTV (per 100 cc’s (OR=1.21, p<0.01)) were also associated with G4L. Sex, age, and BMI were not associated with G4L. Conclusions: Low to intermediate dose volumes to OARs including body, spleen, liver, lungs, and heart were associated with G4L. These findings provide rational for the differences seen in rates of G4L for photon versus proton RT.

Chronic Lymphocytic Leukemia with Bi-Nucleated Lymphocytes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5285-5285 ◽  
Author(s):  
Amin Hrushik ◽  
Lisa Thomas ◽  
Qi Shi ◽  
Sudeep Ruparelia ◽  
Alfonso Zangardi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocyte Count ◽  
Morphological Feature ◽  
Inguinal Lymph Node ◽  
Absolute Lymphocyte Count ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma

Abstract Introduction: B-cell chronic lymphocytic leukemia is one of the common lymphoproliferative disorders in the adult patient population. It is very uncommon to find bi-nucleated lymphocytes as a morphological feature in this disorder. Our patient was diagnosed with CLL and was found to have bi-nucleated lymphocytes in the peripheral smear. The mechanism behind this type of morphological feature of lymphocytes is unknown in CLL, and whether it has prognostic value on disease outcome is undetermined. Case Description: 62 y/o man was referred to hematology oncology after diagnosis of small cell lymphocytic leukemia was made s/p a right inguinal lymph node biopsy. His CBC revealed a wbc count of 14,000, Rbc count of 4,360, Absolute lymphocyte count of 11,500 and Platelet count of 125,000. The patient did not have any B-symptoms. On physical exam, a pertinent finding was palpable right axillary adenopathy. The CT of abdomen /pelvic to evaluate these findings. This revealed extensive axillary, abdominal/pelvic lymphadenopathy, hepatosplenomegaly and cardio phrenic lymphadenopathy. The patient had a biopsy of the right inguinal lymph node as well as bone marrow biopsy. Biopsy results showed small lymphocytic cells, some of which show occasional large nucleoli were consistent with small lymphocytic lymphoma/chronic lymphocytic leukemia, and morphologic characteristics of the lymphocytes showed bi-nucleated lymphocytes in peripheral blood smear (figure A). Flow cytometric analysis confirmed a lymphocytic population with lambda light chain restriction, expressing CD5, CD19, CD20, and CD23 consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. Bone marrow biopsy showed a hypercellular marrow with 75 % cellularity mainly composed of mature lymphocytes with scattered macrophages and eosinophils, Flow cytometric analysis (Clarient FI11-041053) of the bone marrow is interpreted as chronic lymphocytic leukemia/small cell lymphoma with the abnormal B cells representing 56% of the viable white cells. FISH study showed deletion of the ATM gene (11q22-23), D13S319 (13q14) and TP53 (p53) were observed in 29%, 71% and 35.5% of the cells analyzed, respectively. A subset of cells with the 13q deletion (20.5% of the total cells) showed homozygous deletion of D13S319 (13q14). ATM deletion is associated with progressive disease and poor prognosis in cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).He did not have any other previous history of malignancy or hematologic disorder. Discussion: B-cell chronic lymphocytic leukemia is one of the common lymphoproliferative disorders in the adult patient population. To make a diagnosis requires absolute lymphocyte count >4x10 9 and lymphoid cell morphology. In CLL, leukemic cells are small and mature appearing lymphocytes, which have regular nuclear and cytoplasmic outlines and scant weakly basophilic cytoplasm. Surface markers that define a CLL cell are proteins such as antibody light chains (kappa or lambda) and CD proteins (CD5, CD19, CD20, and CD23). In our patient absolute lymphocyte count was 11.5x109 and lymphocytic population showed surface marker lambda light chain and CD proteins CD5, CD19, CD20 and CD23 which was consistent with CLL/SLL on inguinal lymph node biopsy, but morphology of lymphocytes was small and mature bi-nucleated lymphocytes, which is very uncommon. Although bi-nucleated lymphocytes are described in a disorder "Polyclonal chronic B-cell lymphocytosis with bi-nucleated lymphocytes". Detection of an extra chromosome for the long arm of chromosome 3 +i(3)(q10) has been considered a specific marker of Polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL),which was not present in our case. One case study by Amouroux et al, included four patients with B-cell CLL who were found to have bi-nucleated lymphocytes. Disease course was stable in one patient, one patient had an indolent course and only one required treatment due to rapid doubling time of lymphocytes. Our patient initiated chemotherapy with Rituxan and Fludara, as he had progressive disease with hepatosplenomegaly, lymph nodes and bone marrow involvement. Conclusion: Bi -nucleated lymphocytes in B-cell CLL are very rare. Explanations as to the etiology of this morphological feature in B-cell CLL is unknown. There is no sufficient evidence that bi-nucleated lymphocytes in CLL has any impact on disease progression. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of Patients Who May Benefit From Prophylactic Immunotherapy After Bone Marrow Transplantation for Acute Myeloid Leukemia on the Basis of Lymphocyte Recovery Early After Transplantation

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3481-3486 ◽  
Author(s):  
Ray Powles ◽  
Seema Singhal ◽  
Jennifer Treleaven ◽  
Samar Kulkarni ◽  
Clive Horton ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Lymphocyte Count ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Absolute Lymphocyte Count ◽  
Gvhd Prophylaxis ◽  
Risk Of Relapse ◽  
Acute Myeloid

Two hundred and one patients (median age, 29 years) with acute myeloid leukemia (AML) underwent bone marrow transplantation (BMT) from HLA-identical sibling donors after conditioning with melphalan-total-body irradiation (TBI) (57%), cyclophosphamide-TBI (35%), or chemotherapy alone (8%). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine alone (68%), cyclosporine-methotrexate (26%), or T-cell depletion (6%). The probability of relapse was calculated as a function of the absolute lymphocyte count (109/L) on days 27 to 30 posttransplant (<0.1 v ≥0.1, <0.2 v ≥0.2, and <0.3 v≥0.3). In each of these 12 comparisons, the probability of relapse was higher for the group with the lower lymphocyte count. Because the difference was most significant (P = .004) for an absolute lymphocyte count of <0.2 on day 29 (3-year relapse probability, 42%) versus ≥ 0.2 (16%), this variable was included in a Cox model to determine factors independently affecting relapse. Multivariate analysis showed that conditioning regimens other than melphalan-TBI, a low lymphocyte count on day 29, French-American-British (FAB) subtypes M4-7, and a nucleated cell dose of > 2.42 × 108/kg was associated with a higher risk of relapse. We conclude that slow lymphocyte recovery after allogeneic BMT, to < 0.2 × 109/L 29 days in this analysis, appears to be associated with a higher risk of relapse in patients with AML. This group of patients may benefit from posttransplant immune manipulations such as abbreviated GVHD prophylaxis, or donor cell or cytokine administration to enhance graft-versus-leukemia reactions to reduce relapse.

scholarly journals Identification of Patients Who May Benefit From Prophylactic Immunotherapy After Bone Marrow Transplantation for Acute Myeloid Leukemia on the Basis of Lymphocyte Recovery Early After Transplantation

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3481-3486 ◽  
Author(s):  
Ray Powles ◽  
Seema Singhal ◽  
Jennifer Treleaven ◽  
Samar Kulkarni ◽  
Clive Horton ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Lymphocyte Count ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Absolute Lymphocyte Count ◽  
Gvhd Prophylaxis ◽  
Risk Of Relapse ◽  
Acute Myeloid

Abstract Two hundred and one patients (median age, 29 years) with acute myeloid leukemia (AML) underwent bone marrow transplantation (BMT) from HLA-identical sibling donors after conditioning with melphalan-total-body irradiation (TBI) (57%), cyclophosphamide-TBI (35%), or chemotherapy alone (8%). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine alone (68%), cyclosporine-methotrexate (26%), or T-cell depletion (6%). The probability of relapse was calculated as a function of the absolute lymphocyte count (109/L) on days 27 to 30 posttransplant (<0.1 v ≥0.1, <0.2 v ≥0.2, and <0.3 v≥0.3). In each of these 12 comparisons, the probability of relapse was higher for the group with the lower lymphocyte count. Because the difference was most significant (P = .004) for an absolute lymphocyte count of <0.2 on day 29 (3-year relapse probability, 42%) versus ≥ 0.2 (16%), this variable was included in a Cox model to determine factors independently affecting relapse. Multivariate analysis showed that conditioning regimens other than melphalan-TBI, a low lymphocyte count on day 29, French-American-British (FAB) subtypes M4-7, and a nucleated cell dose of > 2.42 × 108/kg was associated with a higher risk of relapse. We conclude that slow lymphocyte recovery after allogeneic BMT, to < 0.2 × 109/L 29 days in this analysis, appears to be associated with a higher risk of relapse in patients with AML. This group of patients may benefit from posttransplant immune manipulations such as abbreviated GVHD prophylaxis, or donor cell or cytokine administration to enhance graft-versus-leukemia reactions to reduce relapse.

scholarly journals Proton Versus Intensity-Modulated Radiation Therapy: First Dosimetric Comparison for Total Scalp Irradiation

2019 ◽  
Vol 6 (3) ◽  
pp. 19-26
Author(s):  
Ankur Markand Sharma ◽  
Emily Kowalski ◽  
Nathan McGovern ◽  
Mingyao Zhu ◽  
Mark Vikas Mishra
Keyword(s):  
Radiation Therapy ◽  
Organs At Risk ◽  
Treatment Plan ◽  
Intensity Modulated Radiation Therapy ◽  
High Dose ◽  
Proton Radiation ◽  
Dosimetric Comparison ◽  
Intensity Modulated ◽  
Volumetric Arc Therapy ◽  
Cutaneous Lymphomas

Abstract Purpose: Total scalp irradiation (TSI) is used to treat malignancies of the scalp and face, including angiosarcomas, nonmelanoma skin cancers, and cutaneous lymphomas. Owing to the irregularity of the scalp contour and the presence of underlying critical organs at risk (OARs), radiation planning is challenging and technically difficult. To address these complexities, several different radiation therapy techniques have been used. These include the combined lateral photon-electron technique (3DRT), intensity-modulated radiation therapy (IMRT)/volumetric arc therapy (VMAT), helical tomotherapy (HT), and mold-based high-dose-rate brachytherapy (HDR BT). However, the use of proton radiation therapy (PRT) has never been documented. Materials and Methods: A 71-year-old, immunosuppressed man presented with recurrent nonmelanoma skin cancer of the scalp. He was successfully treated at our center with PRT to deliver TSI. A comparative VMAT treatment plan was generated and dose to critical OARs was compared. Results: We present the first clinical case report of PRT for TSI and dosimetric comparison to a VMAT plan. The PRT and VMAT plans provided equivalent target volume coverage; however, the PRT plan significantly reduced dose to the brain, hippocampi, and optical apparatus. Conclusion: TSI planned with PRT is relatively straightforward from a planning perspective and does not require a bolus. It also has the potential to decrease radiation therapy–related toxicity. However, PRT is relatively expensive and not universally available. The uncertainty surrounding the end-range of the proton beam is a consideration. Although there are potential disadvantages to using PRT for TSI, its use should be considered by treating radiation oncologists and referring physicians.

Dosimetric Evaluation of Photons Versus Protons in Postmastectomy Planning for Ultrahypofractionated Breast Radiotherapy

2021 ◽  
Author(s):  
Puntiwa Oonsiri ◽  
Chonnipa Nantavithya ◽  
Chawalit Lertbutsayanukul ◽  
Thanaporn Sarsitthithum ◽  
Mananchaya Vimolnoch ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Chest Wall ◽  
Organs At Risk ◽  
Skin Dose ◽  
Proton Radiation ◽  
Breast Radiotherapy ◽  
Left Chest ◽  
Ipsilateral Lung ◽  
Heart Dose ◽  
The Right

Abstract Background: Ultrahypofractionation can shorten the irradiation period. This study is the first dosimetric investigation comparing ultrahypofractionation using volumetric arc radiation therapy (VMAT) and intensity-modulated proton radiation therapy (IMPT) techniques in postmastectomy treatment planning. Materials and methods: Twenty postmastectomy patients (10-left and 10-right sided) were replanned with both VMAT and IMPT techniques. There were 4 scenarios: left chest wall, left chest wall including regional nodes, right chest wall, and right chest wall including regional nodes. The prescribed dose was 26 Gy (RBE) in 5 fractions. For VMAT, a 1-cm bolus was added for 2 in 5 fractions. For IMPT, robust optimization was performed on the CTV structure with a 3-mm setup uncertainty and a 3.5% range uncertainty. This study aimed to compare the dosimetric parameters of the PTV, ipsilateral lung, contralateral lung, heart, skin, esophageal, and thyroid doses. Results: The PTV-D95 was kept above 24.7 Gy in both VMAT and IMPT plans. The ipsilateral lung mean dose of the IMPT plans was comparable to that of the VMAT plans. In three of four scenarios, the V5 of the ipsilateral lung in IMPT plans was lower than in VMAT plans. The Dmean and V5 of heart dose were reduced by a factor of 4 in the IMPT plans of the left side. For the right side, the Dmean of the heart was less than 1 Gy for IMPT, while the VMAT delivered approximately 3 Gy. The IMPT plans showed a significantly higher skin dose owing to the lack of a skin-sparing effect in the proton beam. The IMPT plans provided lower esophageal and thyroid mean dose. Conclusion: Despite the higher skin dose with the proton plan, IMPT significantly reduced the dose to adjacent organs at risk, which might translate into the reduction of late toxicities when compared with the photon plan. Key words: proton therapy, ultrahypofractionation, postmastectomy, breast irradiation

scholarly journals Dosimetric comparison of organs at risk with three-dimensional conformal radiation, intensity-modulated radiation and volumetric-modulated arc therapy in cervical cancer: a cross sectional study

2021 ◽  
Author(s):  
Febin Antony ◽  
Mathew Varghese K. ◽  
Jomon Raphael C. ◽  
Paul Gopu G. ◽  
S. Sivakumar
Keyword(s):  
Cervical Cancer ◽  
At Risk ◽  
Bone Marrow ◽  
Radiation Therapy ◽  
Radiation Exposure ◽  
Organs At Risk ◽  
Volumetric Modulated Arc Therapy ◽  
Three Dimensional ◽  
Intensity Modulated ◽  
Arc Therapy

Three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) are the three main radiotherapy treatment techniques for cervical cancer. Whether either technique significantly reduces the radiation exposure to organs at risk remains unclear. We dosimetrically compared the irradiated volumes of bone marrow, bladder and rectum in cervical cancer patients using 3DCRT, IMRT and VMAT techniques in those patients with FIGO stage IIIB cervical cancer, receiving chemo irradiation at our institute.  A total of 10 patients were dosimetrically compared. Significant reduction in V10, V20, V30, V40, V50 Gy of bone marrow was observed with IMRT and VMAT when compared to 3DCRT. Similar results were seen with V20, V30, V40, V50 Gy of bladder, and V40, V50 Gy of rectum. While comparing IMRT and VMAT, statistically significant dose reduction was noted in V20 Gy of bone marrow and V20 and V30 Gy of bladder with VMAT. When compared with 3DCRT the use of IMRT and/or VMAT reduced the radiation exposure to bone marrow, bladder, and rectum volumes at various radiation dose levels. VMAT can further reduce the radiation exposure to bone marrow and bladder when compared with IMRT. Thus, we propose the use of VMAT in cervical cancer to reduce the OAR toxicities.

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