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Background: Pancreatic cancer is a devastating disease with a 5-year survival rate of 5-10%. Radiation is commonly used in neoadjuvant and adjuvant settings to improve local control. Studies have shown that circulating lymphocyte count depletion after radiation has been associated with poor tumor control and inferior overall survival (OS) outcomes. Method: To better understand the impact of radiation-associated lymphopenia in pancreatic cancer, the authors undertook this systematic review and meta-analysis of clinical studies that have reported radiation-related lymphopenia in pancreatic cancer. Results: A systematic methodology search of PubMed, Embase and the Cochrane Library resulted in 2969 abstracts. Nine studies fulfilled the inclusion criteria. Six studies reported on outcomes in patients undergoing definitive chemoradiation and three studies comparing outcomes in stereotactic body radiotherapy versus definitive chemoradiation. The patients with severe lymphopenia were at increased risk of death with a pooled hazard ratio of 2.33 (95% CI: 1.79, 3.03; I2: 36%; p < 0.001) compared with patients with no severe lymphopenia. The odds of developing severe lymphopenia were 1.12 (95% CI: 0.45, 2.79; I2: 95%; p < 0.81). The pooled mean difference for OS was -6.80 months (95% CI: -10.35, -3.24; I2: 99%; p < 0.002), suggesting that patients who develop grade 3 or 4 lymphopenia have inferior median OS outcomes. Limiting the mean splenic dose to less than 9 Gy as well as various spleen dosimetric parameters such as visit (V)10 <32%, V15 <23% and V20 <15.4% can reduce the incidence of severe lymphopenia. Conclusion: Radiation-related lymphopenia is associated with an increased hazard of death and inferior median OS. Spleen dosimetric parameters correlate with the incidence of severe lymphopenia and with sub-optimal survival outcomes. There is a need to validate these findings in prospective studies.
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Linfopenia , Neoplasias Pancreáticas , Humanos , Contagem de Linfócitos , Linfopenia/etiologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/radioterapia , Estudos Prospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. METHODOLOGY: To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. RESULTS: Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. CONCLUSION: One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.
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Linfopenia/etiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Neoplasias da Bexiga Urinária/radioterapia , Humanos , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/diagnóstico , Masculino , Lesões por Radiação/sangue , Lesões por Radiação/diagnóstico , Radioterapia/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Introduction Acute lymphoblastic leukemia (ALL) constitutes a significant portion of pediatric malignancies, with central nervous system (CNS) relapse posing a considerable threat to patient outcomes. While cranial radiation therapy (CRT) has been utilized to mitigate CNS relapse, it is associated with neurocognitive (NC) side effects. This study explores the feasibility and safety of using volumetric arc therapy (VMAT) with hippocampal sparing (HS) during cranial radiation therapy for ALL patients, aiming to reduce these side effects. Methodology This prospective observational study included pediatric and young adult patients with ALL who were in remission. HS was achieved using VMAT, and NC assessments were performed at baseline, six months, one year, and, to a limited extent, four years posttreatment. Results VMAT enabled precise hippocampal-sparing CRT with minimal dose to the hippocampus. Dosimetric analysis revealed that patients receiving 18 Gy had mean doses to planning target volume (PTV) and bilateral hippocampus of 18.9 and 9 Gy, respectively. Those receiving 12 Gy had corresponding doses of 13.3 and 7 Gy, respectively. Conformity and homogeneity indices were 0.9 and 0.1, and no brain relapses were observed among the patients in this study. NC assessments demonstrated no decline in intelligence quotient (IQ) scores over time, while only a subset of patients could be assessed at the four-year mark; telephone interviews suggested no significant cognitive decline. Conclusions This study highlights the potential of VMAT with HS as a promising approach to CRT for ALL patients in reducing the risk of NC side effects. The absence of brain relapses and preservation of NC function are encouraging findings, though larger studies are necessary to establish conclusive evidence.
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The treatment landscape for localized and regional prostate cancer includes active surveillance, radiation therapy (RT), and radical prostatectomy (RP). Population-based studies comparing RP to radiation reveal conflicting results due to methodological flaws. This systematic review and pooled analysis of studies aim to compare cause-specific survival (CSS), overall survival (OS), disease-free survival (DFS) and toxicity outcomes, comparing RP to RT in the management of prostate cancer. This systematic review search included the PubMed, Embase, and Cochrane libraries according to the PRISMA statement with the inception of each database up to June 24, 2023. Randomized phase 2 or 3 clinical trials that compared RP to RT in prostate cancer were included. The forest plot for the Odds ratio (OR) was plotted using the Mantel-Haenszel method, and the Z test was used to assess significance. A fixed effects model was used for meta-analysis. The search yielded seven completed randomized clinical trials and four ongoing trials. The majority of complete trials had low to intermediate-risk patient populations. OR for OS was 1.00 with 95% CI, 0.71-1.41 (P-value: 0.98), CSS OR was 0.99 with 95% CI, 0.45-2.18 (P-value 0.11), OR for DFS was 1.26 with 95% CI, 0.89-1.78 (P-value 0.19) when comparing RP to RT. The rate of distant metastatic disease was 2.3% in the RP versus 2.9% in the RT at 10 years. The rate of second malignant neoplasms was 4.5% in the RP compared to 4.2% in the RT arm at 10 years. RP caused more urinary symptoms, with a predominance of the need for urinary pads and a higher incidence of sexual dysfunction, and RT caused a higher incidence of bowel symptoms, such as blood in stools and fecal incontinence. This study provides evidence that the treatment-related outcomes are similar in patients with low to intermediate-risk prostate cancer when comparing RP to RT. Multidisciplinary treatment approaches and factoring patients' values and preferences should form the cornerstone of the ideal treatment option for each patient with localized prostate cancer. Patients with prostate cancer have an equal chance of being cancer-free and alive at 10 years with either RP or RT. In terms of side effects, RP causes more urine leakage and loss of erections, whereas RT tends to cause more bowel side effects, such as blood in stools and fecal leakage.
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Radical cystectomy is long considered as the "gold standard" in the management of localized muscle-invasive bladder cancer (MIBC), and curative intent radiotherapy is relegated to those with either inoperable tumors or with multiple co-morbidities precluding surgery. This is despite a large volume of data showing equal survival between the two modalities of treatment in this setting. In this work we seek to dispel some common myths surrounding curative intent radiotherapy as part of a bladder preservation strategy in MIBC. Baseless claims of inferior outcomes and perceived contraindications for bladder preservation are debunked along with unfounded doubts relating to hypofractionation. Finally, we caution against using response to neoadjuvant chemotherapy as a predictive biomarker for treatment selection and conclude by recommending that trimodality bladder preservation be offered as a therapeutic option that is in clinical equipoise with radical cystectomy.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgia , Cistectomia , Terapia Neoadjuvante , Músculos/patologiaRESUMO
The need for axillary radiotherapy in patients with invasive breast cancer (IBC) has been a topic of great debate in the last decade. Management of the axilla has evolved significantly over the past four decades with a trend towards de-escalation of surgical interventions and the aim of reducing morbidity and enhancing QOL without compromising long-term oncology outcomes. This review article will address the role of axillary irradiation with a focus on the omission of completion axillary lymph node dissection in selected patients with sentinel lymph node (SLN) positive early breast cancer (EBC) with reference to current guidelines based on evidence to date.
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PURPOSE: Bladder-sparing trimodal therapy (TMT) is an alternative to radical cystectomy (RC) according to international guidelines. However, there are limited data to guide management of nonmetastatic clinically node-positive bladder cancer (cN+ M0 BCa). We performed a multicenter retrospective analysis of survival outcomes in node-positive patients to inform practice. METHODS: Data from patients diagnosed with cN+ M0 BCa were collected from participating UK Oncology centers offering both TMT and RC. Overall survival (OS) and progression-free survival (PFS) outcomes were collected with details of treatment and clinical factors. RESULTS: A total of 287 patients with cN+ M0 BCa were included in the survival analysis. Median OS across all patients was 1.55 years (95% CI, 1.35 to 1.82 years). Receiving radical treatments was associated with improved OS (hazard ratio [HR], 0.32; 95% CI, 0.23 to 0.44; P < .001) compared with receiving palliative treatment. Radically treated patients (n = 163) received RC (n = 76) or radical dose radiotherapy (RT, n = 87); choice of radical treatment showed no association with OS (HR, 0.94; 95% CI, 0.63 to 1.41; P = .76) or PFS (HR, 0.74; 95% CI, 0.50 to 1.08; P = .12) on multivariable analysis. CONCLUSION: Patient cohorts with cN+ M0 BCa had equivalent survival outcomes whether treated with surgery or radical RT. Given the known morbidities of RC-in a patient group with poor survival-this study confirms that bladder-sparing TMT treatment should be a treatment option available to all patients with cN+ M0 BCa.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
PURPOSE: To evaluate clinical outcomes for cN1M0 prostate cancer treated with varied modalities. MATERIALS AND METHODS: Men with radiological stage cN1M0 prostate cancer on conventional imaging, treated from 2011-2019 with various modalities across four centres in the UK were included. Demographics, tumour grade and stage, and treatment details were collected. Biochemical and radiological progression-free survival (bPFS, rPFS) and overall survival (OS) were estimated using Kaplan Meier analyses. Potential factors impacting survival were tested with univariable log-rank test and multivariable Cox-proportional hazards model. RESULTS: Total 337 men with cN1M0 prostate cancer were included, 47% having Gleason grade group 5 disease. Treatment modalities included androgen deprivation therapy (ADT) in 98.9% men, either alone (19%) or in combinations including prostate radiotherapy (70%), pelvic nodal radiotherapy (38%), docetaxel (22%), or surgery (7%). At median follow up of 50 months, 5-year bPFS, rPFS, and OS were 62.7%, 71.0%, and 75.8% respectively. Prostate radiotherapy was associated with significantly higher bPFS (74.1% vs 34.2%), rPFS (80.7% vs 44.3%) and OS (86.7% vs 56.2%) at five years (log rank p < 0.001 each). On multivariable analysis including age, Gleason grade group, tumour stage, ADT duration, docetaxel, and nodal radiotherapy, benefit of prostate radiotherapy persisted for bPFS [HR 0.33 (95% CI 0.18-0.62)], rPFS [HR 0.25 (0.12-0.51)], and OS [HR 0.27 (0.13-0.58)] (p < 0.001 each). Impact of nodal radiotherapy or docetaxel was not established due to small subgroups. CONCLUSION: Addition of prostate radiotherapy to ADT in cN1M0 prostate cancer yielded improved disease control and overall survival independent of other tumour and treatment factors.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Próstata/patologia , Estudos Retrospectivos , Intervalo Livre de Doença , DocetaxelRESUMO
Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I 2 = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I 2 = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I 2 = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.
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OBJECTIVE: To assess the change in the quality of life (QOL) in head and neck cancer patients treated with Simultaneous Integrated Boost (SIB) by Volumetric Modulated Arc Therapy (VMAT) technique. METHODS: Thirty patients with localised head and neck cancers (Stage II- IVa) were treated with VMAT and SIB technique. The three-dose levels prescribed were 68.2â¯Gy at 2.2â¯Gy/fraction, 62â¯Gy at 2â¯Gy/fraction and 55.8â¯Gy at 1.8â¯Gy/fraction to the high, intermediate and low-risk volumes respectively. Concurrent chemotherapy with cisplatin 100â¯mg/m2 was administered once in three weeks. Acute toxicities were evaluated and scored according to the RTOG grading system. Quality of life (QOL) was assessed using European Organization of Research and Treatment of Cancer (EORTC) QLQC30 and HN35 questionnaires at baseline and in three instances (immediately, one month and three months after the radiotherapy). RESULTS: Out of the total 30, 80% patients had a complete response (CR) at the median follow up of 12â¯months, while three patients died because of progression, and the remaining 3 had stable disease. All planning objectives were achieved for organs at risk and planning target volume(PTV). There was a statiscally significant(p valueâ¯<â¯0.001) reduction in global quality of life scores at the end of treatment when compared to baseline scores, but by three months, there was the return in the QOL scores in most scales similar to the baseline value. CONCLUSION: VMAT based Simultaneous boost radiotherapy is a feasible and safe strategy in terms of toxicity profile with an acceptable transient change in the quality of life and allows a faster return to baseline quality of life.
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BACKGROUND: Despite the modern advances in treatment techniques, the survival of locally advanced lung cancer patients continues to remain poor. Circulating lymphocytes have an important role to play in local immune response to RT as well as immune checkpoint inhibitors, and radiation related lymphopenia has been associated with inferior survival in various tumors. METHODS: We undertook this systematic review and meta-analysis to evaluate the literature on risk and impact of lymphopenia in thoracic tumors. A systematic methodology search of the PubMed, Embase and Cochrane library was performed and eligible studies selected based on pre-defined inclusion and exclusion criteria. Review Manager Version 5.4.1 was used for the meta-analysis. RESULTS: Fourteen studies were included in the final systematic review and 10 in the quantitative analysis. Overall mean incidence of severe lymphopenia (absolute lymphocyte count < 500) was 64.24%. The patients with severe lymphopenia were at increased risk of death with a pooled HR of 1.59 (95% CI: 1.40, 1.81, I2 = 17%, P < 0.001) and progression with a pooled HR of 2.1 (95% CI: 1.57, 2.81, I2 = 59%, P < 0.001) compared to patients with no severe lymphopenia. Dosimetric parameters including gross tumor volume, lung V5 and heart V5 were predictive of lymphopenia, while advanced age, lower baseline lymphocyte counts, higher stage and large tumor size were other risk factors. Models predicting estimated radiation dose to lymphocytes were a good surrogate for treatment outcomes. CONCLUSION: Radiation related lymphopenia is associated with increased hazard of progression and death in lung cancer. Minimizing the lung and heart dose, especially in patients with concurrent other risk factors can reduce lymphopenia and potentially improve treatment outcomes in these patients.
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Neoplasias Pulmonares , Linfopenia , Humanos , Pulmão , Neoplasias Pulmonares/radioterapia , Contagem de Linfócitos , Linfócitos , Linfopenia/etiologiaRESUMO
BACKGROUND: Cancer patients with coronavirus disease 2019 (COVID-19) have been reported to have double the case fatality rate of the general population. METHODS: A systematic search of PubMed, Embase, and Cochrane Central was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio (OR) and forest plots (random-effects model) were constructed for both primary and secondary outcomes. RESULTS: This systematic review of 38 studies and meta-analysis of 181 323 patients from 26 studies included 23 736 cancer patients. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (n = 165 980, OR = 2.54, 95% confidence interval [CI] = 1.47 to 4.42), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated. Among cancer subtypes, the mortality was highest in hematological malignancies (n = 878, OR = 2.39, 95% CI = 1.17 to 4.87) followed by lung cancer (n = 646, OR = 1.83, 95% CI = 1.00 to 3.37). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of comorbidities. There was insufficient data to assess the association of COVID-19-directed therapy and survival outcomes in cancer patients. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.