Early Stage Carcinoma of the Uterine Cervix Effects of Intracavitary Radium Treatment on Lymphoid Cells in Blood and Pelvic Lymph Nodes

Onsrud, Mathias; Grahm, Irmelin; Gaudernack, Gustav

doi:10.3109/02841868609136390

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…31 Publications from the 1960s and 1970s noted the development of severe lymphopenia after radiation in patients with brain, breast, cervical, uterine, and lung cancers without the use of concurrent chemotherapy or glucocorticoids. 13,14,16,17,32 The radiation oncologists reporting these results expressed concerns that radiation-induced injury to the immune system could negatively affect patient outcomes, but no attempts were made to correlate posttreatment lymphopenia with survival. Nonetheless, accumulating data suggested that postradiation lymphopenia could result from the irradiation of circulating lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Grossman

Ellsworth

Campian³

et al. 2015

J Natl Compr Canc Netw

250

191

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Background The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival. Materials and Methods Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed. The data set included 297 patients with newly diagnosed malignant glioma (N=96), resected pancreatic cancer (N=53), unresectable pancreatic cancer (N=101), and non–small cell lung cancer (N=47). Results Pretreatment lymphocyte counts were normal in 83% of the patient population, and no patient had severe baseline lymphopenia. Two months after initiating chemoradiation, 43% developed severe and persistent lymphopenia (P=.001). An increased risk for death was attributable to TRL in each cancer cohort (gliomas: hazard rate [HR], 1.8; 95% CI, 1.13–2.87; resected pancreas: HR, 2.2; 95% CI, 1.17–4.12; unresected pancreas: HR, 2.9; 95% CI, 1.53–5.42; and lung: HR, 1.7; 95% CI, 0.8–3.61) and in the entire study population regardless of pathologic findings (HR, 2.1; 95% CI, 1.54–2.78; P<.0001). Severe TRL was observed in more than 40% of patients 2 months after initiating chemoradiation, regardless of histology or chemotherapy regimen, and was independently associated with shorter survival from tumor progression. Conclusions Increased attention and research should be focused on the cause, prevention, and reversal of this unintended consequence of cancer treatment that seems to be related to survival in patients with solid tumors.

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Section: Discussionmentioning

confidence: 99%

“…13–17 These observations were accompanied by concerns that this iatrogenic immunosuppression could interfere with the body’s ability to identify and destroy tumor cells. 13,18 However, until recently, the lymphopenia observed after antineoplastic therapy was not formally associated with inferior patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Grossman

Ellsworth

Campian³

et al. 2015

J Natl Compr Canc Netw

250

191

View full text Add to dashboard Cite

show abstract

“…The pivotal role of immune surveillance against neoplasms is well known . However, immunosuppression elicited by therapy is frequently observed in patients with various malignancies, such as those of the pancreas, breast, uterine cervix, and brain . This iatrogenic lymphopenia was not taken seriously until subsequent evidences indicated that patients with lowered peripheral lymphocyte counts (PLCs) suffered early death from tumor progression .…”

Section: Introductionmentioning

confidence: 99%

Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy

Fan

et al. 2019

Cancer Medicine

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Background The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity‐modulated radiotherapy (IMRT). Methods A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109/L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). Results Sixty‐nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high‐grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. Conclusions HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

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“…Radiation therapy (RT) probably contributes directly to treatment-induced lymphopenia in cancer patients, as lymphopenia occurs after RT regardless of whether other lymphotoxic agents, such as corticosteroids or certain chemotherapeutics (eg, temozolomide) are given (5–7). A proposed mechanism for radiation-induced lymphopenia (RIL) is irradiation of circulating blood, because lymphopenia occurs even after irradiation of tissues such as the breast and the brain, which contain little bone marrow or lymphatic tissue, respectively (6, 8).…”

Section: Introductionmentioning

confidence: 99%

Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer

Wild

Herman

Dholakia

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

187

114

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Purpose Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). Methods and Materials Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 × Gy 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. Results Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm3) than in CRT (344.6 cm3; P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm3 vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310–3.237; P=.002). Conclusions SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted.

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Early Stage Carcinoma of the Uterine Cervix Effects of Intracavitary Radium Treatment on Lymphoid Cells in Blood and Pelvic Lymph Nodes

Cited by 12 publications

References 15 publications

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy

Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer

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