Use Of Prophylactic Cranial Irradiation Research Articles

Real-life clinical management patterns in extensive-stage small cell lung cancer across France: a multi-method study

BackgroundWe designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice.MethodsA 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers.ResultsIn ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2–7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI.ConclusionsThere is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting.

171 - The end of an era? Reduction in the use of prophylactic cranial irradiation (PCI) in limited disease small cell lung cancer (LD SCLC)

171 - The end of an era? Reduction in the use of prophylactic cranial irradiation (PCI) in limited disease small cell lung cancer (LD SCLC)

Survey of treatment and care practices in small-cell lung cancer among German radiation oncologists

BackgroundThe management of small-cell lung cancer shows differences, particularly with regard to the use of radio- (RT), chemo-, and immunotherapy. We performed a survey among German radiation oncologists to assess the management of small-cell lung cancer (SCLC).MethodsA 34-question online survey was created and sent out by e‑mail to radiation oncologists throughout Germany. The survey period extended from August 2020 to January 2021. The questions addressed indications for RT, planning techniques, dosing/fractionation, target volume definition for consolidative thoracic irradiation, and the use of prophylactic cranial irradiation (PCI). At the same time, we surveyed the use of atezolizumab. The survey addressed the treatment practice for limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC).ResultsWe received 74 responses. In LS-SCLC, treatment is planned predominantly based on diagnostic information from computed tomography (CT) of the thorax/abdomen/pelvis (88%), PET-CT (86%), and pulmonary function testing (88%). In LS-SCLC, 99% of respondents perform radiation concurrently with chemotherapy, preferably starting with cycle one or two (71%) of chemotherapy. The most common dose and fractionation schedule was 60–66 Gy in 30–33 fractions (once daily: 62% of all respondents). In ES-SCLC, 30 Gy in 10 fractions (once daily: 33% of all respondents) was the most commonly used regimen in consolidative thoracic irradiation. Only 25% use chemosensitization with RT. The inclusion criteria for PCI were similar for limited and extensive disease, with Karnofsky index (78% and 75%) being the most important decision factor. Respondents use a schedule of 30 Gy in 15 fractions most frequently in both stages (68% limited stage [LS], 60% extensive stage [ES]). Immunotherapy was used regularly or occasionally in LS-SCLC by 45% of respondents, with reduced lung function (37%), cardiac comorbidities (30%), and hepatic insufficiency (30%) being the most commonly mentioned exclusion criteria for this form of therapy. In ES-SCLC, atezolizumab use was reported in 78% of all questionnaires. Half of the respondents (49%) administer it simultaneously with cranial irradiation.ConclusionOur survey showed variability in the management of SCLC. Results from future studies might help to clarify open questions regarding the optimal treatment paradigms. In addition, new treatment modalities, such as immunotherapy, might change practices in the near future.

[Report of Chinese Children's Cancer Group acute lymphoblastic leukemia 2015 multicenter study].

Objective: To evaluate the outcomes and identify the prognostic factors of childhood acute lymphoblastic leukemia (ALL) treated with Chinese Children's Cancer Group study ALL-2015 (CCCG-ALL-2015) protocol. Methods: There were two randomization studies in CCCG-ALL-2015 study. A total of 7 640 newly diagnosed ALL patients in 20 hospitals of multi-institutional study group between January 2015 and December 2019 were treated with unified protocol. CCCG-ALL-2015 protocol featured risk-directed therapy based on morphology, immunophenotype, and genetic features, and adjusted according to minimal residual disease (MRD) assay on day 19 and day 46 of induction, which totally omitted prophylactic cranial irradiation. Two randomized controlled trails were designed. Children with Philadelphia chromosome-positive ALL (Ph+ALL) were randomly treated with dasatinib (Ph-D group) or imatinib (Ph-I group). During the latter half of continuation therapy, children were randomly treated with seven pulses of vincristine plus dexamethasone (group A) or not (group B). The survival rates of different groups were compared. Event-free survival (EFS) and overall survival (OS) curves were estimated according to the Kaplan-Meier method and compared by Log-rank test. Cox proportional hazards model was used for multivariate analysis. Results: Of the 7 640 enrolled patients, there were 4 521 males and 3 119 females, 7 508 (98.3%) entered complete remission. The 5-year EFS was 60.1% (95%CI 49.8%-72.5%) in the Ph-D group and 39.4% (95%CI 26.9%-57.7%) in the Ph-I group (χ2=5.00, P=0.020). Between patients with lower risk (LR) and intermediate and higher risk (I/HR) treated with (group A) or without (group B) additional pulse of vincristine plus dexamethasone, there were no difference in 5-year EFS and OS. The one-sided 95% upper confidence bound for the difference in 5-year EFS and OS were 0.02 and 0.01 for LR, 0.05 and 0.01 for I/HR, establishing non-inferiority, lower than 0.05. The follow-up time was 3.5 (2.4,4.8) years. The 5-year OS was 90.9% (95%CI 90.2%-91.7%), and EFS was 80.1% (95%CI 79.0%-81.2%). The 5-year cumulative risk of any relapse was 15.3% (95%CI 14.3%-16.3%).The cumulative risk of isolated central nervous system (CNS) relapse was 1.9% (95%CI 1.6%-2.2%), and any CNS relapse 2.7% (95%CI 2.3%-3.1%). The 5-year cumulative risk of death during remission was 1.3% (95%CI 1.0%-1.6%). In the multivariate analysis, the independent factors associated with inferior EFS of patients with B-ALL were age≥10 years, male sex, white blood cell count ≥50×109/L, CNS2 or CNS3 status, BCR-ABL fusion, KMT2A rearrangements, without ETV6-RUNX1 fusion and the presence of MRD>0.01% at day 19 or 46 (all P<0.05). Among patients with T-ALL, the significant predictors for lower EFS were the BCR-ABL1 fusion and MRD≥0.10% at day 46 (both P<0.05). Conclusions: Patients treated with CCCG-ALL-2015 protocol without the use of prophylactic cranial irradiation have favorable outcomes, and the cumulative risk of isolated CNS relapse and cumulative risk of death during remission are low. Intensive chemotherapy including dasatinib yield superior results compared to imatinib in the treatment of Ph+ALL. Vincristine plus dexamethasone pulses can be omitted for ALL children without decrease in treatment ontcome during the latter half of continuation therapy.

An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer – A Mainstay of Treatment or a Modality in Decline?

AimsSmall cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC. Materials and methodsThe search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. ClinicalTrials.gov was also queried for relevant trials. ResultsThoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era. ConclusionRadiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients.

EP14.01-014 Risk Factors for Brain Metastasis in Patients with Small Cell Lung Cancer: A Systematic Review and Meta-analysis

The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) is controversial. Risk factors for brain metastasis (BM) are largely unknown, hampering personalized treatment strategies. This study aimed to identify possible risk factors for BM in SCLC.

P7-1 Overall survival with the use of prophylactic cranial irradiation in limited stage-SCLC: A systematic review

Small-cell lung cancer (SCLC) is a form of neuroendocrine carcinoma which has an exceptionally poor prognosis and arises predominantly in smokers. One type of SCLC is limited-stage SCLC (LS-SCLC) which confines the disease within a single, tolerable radiation portal. Brain metastasis is often secondary to LS-SCLC, and the leading cause of morbidity. The use of Prophylactic Cranial Irradiation (PCI) with combined therapy reduces the risk of brain metastasis. This review is to re-evaluate the overall survival (OS) of PCI in comparison with non-PCI patients with LS-SCLC.

Use of prophylactic cranial irradiation in patients with extensive-stage small cell lung cancer receiving immunotherapy.

e19309 Background: Prophylactic cranial irradiation (PCI) use is controversial in extensive-stage small cell lung cancer (ES-SCLC). In addition to lack of survival benefit of PCI compared to close MRI surveillance in a 2017 published trial, the role of PCI is being further challenged in the modern immune-oncology (IO) era. The IMpower133 trial reporting a survival benefit to atezolizumab for ES-SCLC published in 2018 did not require PCI use. Contemporary practice patterns of PCI in relation to immunotherapy are unknown. Methods: We performed a retrospective cohort analysis of patients with ES-SCLC diagnosed between January 1, 2013 to September 31, 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database. First-line chemotherapy (Chemo) was defined as Chemo given alone, while first-line IO therapy was IO alone or combined with chemotherapy as initial systemic therapy. Results: The cohort included 3047 ES-SCLC patients who received first-line Chemo, and 324 patients who received first-line IO. For first-line IO patients, 268 (82.7%) received first-line atezolizumab. The use of first-line IO increased from 1.2% of patients diagnosed in 2013 to 11.3% of patients diagnosed in 2018 (p &lt; 0.001), and 54.5% of patients diagnosed in 2019 (p &lt; 0.001). Overall documented PCI for patients receiving either first-line IO or first-line Chemo decreased from 14.7% in 2013 to 7.0% in 2018-2019 (p &lt; 0.001). For first-line IO patients, 23 (7.1%) had documented PCI over our study period, with 5.3% of patients diagnosed in 2018-2019 having received PCI. In contrast, for first-line Chemo patients, 428 (14.0%) received PCI over our study period, and PCI use significantly decreased from 14.8% in 2013 to 7.9% in 2018-2019 (p = 0.001). In 2018-2019, use of PCI was not significantly different between patients receiving first-line IO compared to first-line Chemo (5.3% vs 7.9%, p = 0.163). Conclusions: The use of first-line IO has significantly increased in ES-SCLC. Overall PCI rates for ES-SCLC patients decreased significantly over the study period, although documented PCI use rates do not differ between patients receiving upfront IO or Chemo in 2018-2019. Further investigation is warranted regarding effectiveness of PCI in the modern IO era.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

PurposeTo identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methodsAmong 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. ResultsMedian follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). ConclusionThree prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended.

Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

A randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups. Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation. Chinese Clinical Trial Registry: ChiCTR-IPR-14005706.

Effect of Dasatinib Vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized, Open-Label, Multicenter Study of the Chinese Children's Cancer Group

OBJECTIVE To determine whether dasatinib given at 80 mg/m2 is more effective than imatinib at 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL, in the context of intensive chemotherapy without prophylactic cranial irradiation. DESIGN, SETTING, AND PARTICIPANTS This open-label phase III randomized study was conducted at 20 hospitals in China. Enrollment began in January 2015 and randomization was stopped in October 2018 when the early stopping criterion of the trial was met. Patients aged between 0 and 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined and 1 died before treatment. INTERVENTIONS Patients were randomized to receive daily dasatinib (n=92) or imatinib (n=97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. MAIN OUTCOMES AND MEASURES The primary outcome was event-free survival, analyzed by intent-to-treat. The secondary outcomes were relapse, toxic death, and overall survival. RESULTS With a median follow-up of 26.1 months (IQR 16.3-34.1), the 4-year event-free survival rate was 71.0% (95% CI 56.2-89.6) in the dasatinib group and 48.9% (95% CI 32.0-74.5, p=0.005) in the imatinib group (hazard ratio 2.36, 95% CI 1.27-4.40, p=0.007). The 4-year cumulative risk of any relapse was 19.8% (95% CI 4.2-35.4) in the dasatinib group and 34.4% (95% CI 15.6-53.2) in the imatinib group (p=0.01), while the 4-year cumulative risk of an isolated central-nervous-system relapse was 2.7% (95% CI 0.0-8.1) in the dasatinib group and 8.4% (95% CI -1.2-15.6) in the imatinib group (p=0.06). There were no significant differences in the frequency of severe toxicities between the two treatment groups. CONCLUSION AND RELEVANCE Intensive chemotherapy including dasatinib at 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared to imatinib at 300 mg/m2 per day and provided excellent control of central-nervous-system leukemia without the use of prophylactic cranial irradiation. Disclosures No relevant conflicts of interest to declare.

Risk Stratification of Symptomatic Brain Metastases By Clinical and FDG PET Parameters for the Selective Use of Prophylactic Cranial Irradiation in Patients with Extensive Disease of Small Cell Lung Cancer

The role of prophylactic cranial irradiation (PCI) remains controversial in extensive disease small cell lung cancer (ED-SCLC). This study is performed to identify the risk factors of symptomatic brain metastasis and to evaluate the impact of PCI on brain metastasis-free survival (BMFS) and overall survival (OS) according to the risk of symptomatic brain metastasis in ED-SCLC. From 2006 to 2017, a total of 190 patients diagnosed with ED-SCLC who underwent FDG-PET and brain MRI prior to treatment were enrolled in this retrospective study. Among these patients, 53 (27.9%) received PCI and 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastasis was calculated in the observation group (137/190) on Cox regression model and the prognostic index was generated by summating significant factors weighted by a hazard ratio of each. The role of PCI in each risk group was analyzed by using Kaplan-Meier survival analysis. Median follow-up time was 10.6 months. 1-year and 2-year symptomatic BMFS were 86.9% and 49.8%, and 1-year and 2-year OS were 52.5% and 12.7%, respectively. Multivariate Cox regression analysis showed that 4 risk factors were associated with high risk of symptomatic brain metastasis: presence of extrathoracic metastases (P = 0.005) and hypermetabolism of bone marrow (BM) or spleen (P < 0.001) on FDG PET, as well as progressive disease (PD) after chemotherapy (P = 0.010) and high hemoglobin (Hb) level (P = 0.006). The prognostic index significantly divided patients into two subgroups of high and low-risk of symptomatic brain metastasis (P < 0.001). PCI significantly improved BMFS in high-risk patients (P = 0.002, 1-year rate 95.5% vs. 61.8%), but not in low-risk patients (P = 0.522, 1-year rate 100.0% vs. 91.9%). However, PCI did not improve OS in patients at high risk for symptomatic brain metastasis (P = 0.801, 1-year rate 45.0% vs. 50.0%). Four prognostic factors are associated with a high risk of symptomatic brain metastasis in ED-SCLC: the presence of extrathoracic metastases, hypermetabolism of BM or spleen from FDG PET parameters, PD after chemotherapy and high Hb level. PCI was beneficial for patients at high risk of symptomatic brain metastasis in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification by the prognostic factors from FDG PET and clinical parameters may be recommended, after the completion of a further validation study with a prospective manner.

Evolving Practice Patterns in the Use of Prophylactic Cranial Irradiation for Extensive-Stage Small Cell Lung Cancer

Evolving Practice Patterns in the Use of Prophylactic Cranial Irradiation for Extensive-Stage Small Cell Lung Cancer

The Impact of the Stage III Randomized Trial by Takahashi et al. on the Use of Prophylactic Cranial Irradiation (PCI) in Patients with Extensive-Stage Small-Cell Lung Cancer (ES-SCLC)

The Impact of the Stage III Randomized Trial by Takahashi et al. on the Use of Prophylactic Cranial Irradiation (PCI) in Patients with Extensive-Stage Small-Cell Lung Cancer (ES-SCLC)

Prognostic Significance of Total Lymphocyte Count, Neutrophil-to-lymphocyte Ratio, and Platelet-to-lymphocyte Ratio in Limited-stage Small-cell Lung Cancer

BackgroundWe sought reliable markers of survival and disease control among patients treated for limited-stage small-cell lung cancer (LS-SCLC). Patients and MethodsSubjects were 122 patients given (chemo)radiotherapy for LS-SCLC at MD Anderson in 2002 through 2015. Pretreatment total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed for associations with overall (OS) and progression-free survival. Optimal cutoff values were identified with receiver operating characteristic curves and survival probabilities with the Kaplan-Meier method. ResultsPretreatment TLC was 1.86 × 103/μL (±0.88); NLR, 3.44 (±3.69); and PLR, 170.53 (±101.56); corresponding cutoffs were 1.9, 2.9, and 140.1. Higher TLC was associated with superior median and 2-year OS (17.4 vs. 15.7 months and 33% vs. 29%; P = .029), and higher NLR and PLR with worse median and 2-year OS (NLR: 14.9 vs. 17.8 months, 29% vs. 31%; P = .026; PLR: 14.8 vs. 18.9 months, 24% vs. 37%; P = .009). Multivariate Cox regression adjusted for age, disease stage, number of chemotherapy cycles, and use of prophylactic cranial irradiation confirmed the links between high TLC and superior OS (hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.32-0.94; P = .028) and between high NLR and PLR and inferior OS (NLR: HR, 1.86; 95% CI, 1.15-3.01; P = .011; PLR: HR, 1.72; 95% CI, 1.06-2.82; P = .030). ConclusionsBaseline lymphopenia was an indicator of poor prognosis in patients with LS-SCLC.

The Use of Prophylactic Cranial Irradiation (PCI) and Consolidative Thoracic Radiation (TRT) in Extensive Stage Small Cell Lung Cancer (ES-SCLC) in the United States (US) and its Survival Benefit

The role of PCI and TRT in ES-SCLC remains controversial. While the European study showed benefit of PCI in this disease, a Japanese study showed no such survival improvement. Similarly, addition of TRT also has conflicting results making it difficult to adopt in common practice. We aimed to review the practice pattern of using PCI and TRT in the US and whether it improves overall survival following initial chemotherapy. We analyzed National cancer database to identify patients with stage IV (ES-SCLC) disease diagnosed between 2004-2014. Patients with brain metastasis at diagnosis and who died within 30 days from diagnosis were excluded. 19% (n=5988) who did not receive any chemotherapy, 2% (n=721) who had single agent chemotherapy were excluded. 73% (n=23,458) patients received multiagent chemotherapy and were included (n=23,458; 73%) in this analysis. Statistical significance was defined as p≤.05 using statistical software. The median age was 67 years (21-90 years) with median follow up of 9 months (2-70 months). 50% patients were male. Majority of patients (n=14,439, 87%)) did not receive any radiation, 13% (n=2217) received PCI and 19% (n=4363) received TRT, while 9% (n=2130) patients received other palliative radiation. Addition of PCI and TRT improved median survival, 1 year and two years survival significantly (Table 1).Tabled 1Abstract TU_38_3701; Table 1 Survival difference with and without PCI and TRTSurvivalPCINo PCITRTNo TRTp-valueMedian survival (months)12.758.5111.438.51<.0011-year OS52.59%26.74%44.83%26.74%<.0012-year OS13.12%6.0%15.56%6%<.001 Open table in a new tab This hospital-based registry analysis shows that PCI and TRT are not commonly utilized for ES-SCLC in patients who otherwise were treated with multiagent chemotherapy. However, this study shows significant OS benefit with addition of PCI and TRT in this otherwise poor prognostic group. Further research is needed to confirm the role of PCI and TRT especially in the era of improved systemic therapy.

Strategies to Preserve Cognition in Patients With Brain Metastases: A Review.

Brain metastases are common to the natural history of many advanced malignancies. Historically, whole brain radiation therapy (WBRT) has played a key role in the management of brain metastases, especially for patients with multiple lesions. However, prospective trials have demonstrated consistent neurocognitive toxicities after WBRT, and various pharmacologic and anatomic strategies designed to mitigate these toxicities have been studied in recent years. Memantine, an NMDA receptor antagonist, taken during and after WBRT improved cognitive preservation in a randomized trial over placebo. Deliberate reductions in radiation dose to the hippocampus, via hippocampal-avoidance (HA)-WBRT, resulted in improved cognition over historic controls in a phase II trial, and follow-up randomized trials are now ongoing to evaluate cognitive outcomes with HA vs. conventional brain radiation techniques. Nevertheless, some of the most promising strategies currently available to reduce the cognitive effects of brain radiation may be found in efforts to avoid or delay WBRT administration altogether. Stereotactic radiosurgery (SRS), involving focused, high-dose radiation to central nervous system (CNS) lesions with maximal sparing of normal brain parenchyma, has become the standard for limited brain metastases (classically 1–3 or 4 lesions) in the wake of multiple randomized trials demonstrating equivalent survival and improved cognition with SRS alone compared to SRS plus WBRT. Today, there is growing evidence to support SRS alone for multiple (≥4) brain metastases, with comparable survival to SRS alone in patients with fewer lesions. In patients with small-cell lung cancer, the routine use of prophylactic cranial irradiation (PCI) for extensive-stage disease has been also been challenged following the results of a randomized trial supporting an alternative strategy of MRI brain surveillance and early salvage radiation for the development of brain metastases. Moreover, new systemic agents are demonstrating increasing CNS penetration and activity, with the potential to offer greater control of widespread and microscopic brain disease that was previously only achievable with WBRT. In this review, we endeavor to put these clinical data on cognition and brain metastases into historical context and to survey the evolving landscape of strategies to improve future outcomes.

PC02.03 BID Radiation - CON

Thoracic radiotherapy for LS-SCLC: QD is just as good as BID? Most of the advances in outcome of small cell lung cancer (SCLC) in the past few decades can be attributed to improvements in radiotherapy, including better imaging and target selection, better treatment planning, better integration with chemotherapy, and use of prophylactic cranial irradiation. Thoracic radiotherapy plays an important role in the treatment of limited disease SCLC (LS-SCLC). Best results are obtained with twice daily (BID) radiotherapy, starting early and given concurrently with chemotherapy [1]. In addition, it was shown that a shorter time from start of chemotherapy to completion of radiotherapy was associated with longer survival [2]. Two meta-analyses demonstrated that use of thoracic radiotherapy led to improved local control and an absolute survival benefit at 3 years of 5% [3,4]. Turrisi et al. [5] demonstrated in the Intergroup 0096 study that 45 Gy given BID in 30 fractions in 3 weeks was superior compared to the same dose delivered once-daily (QD) in 25 fractions over a 5 week period. Overall survival at 5 years was improved (26% vs 16%), but at the expense of more G3-4 oesophagitis (32 vs 16%). In spite of these results, BID radiotherapy is still used in a only a minority of SCLC patients [6,7]. In The Netherlands, early concurrent BID radiotherapy is given in about a quarter of the patients [7]. The radiotherapy dose in the QD arm of the Intergroup trial [5] was relatively low and some argued that a higher QD radiotherapy dose might be equivalent to or even better than the 45 Gy BID scheme. In the ongoing CALGB 30610 / RTOG 0538 study (NCT00632853) a dose of 70 Gy once-daily in 35 fractions in 7 weeks is compared with the 45Gy BD scheme. In this trial, radiotherapy starts with the first course of chemotherapy and includes elective nodal irradiation. Accrual is expected to continue for several years. In the recently published CONVERT trial (ISRCTN91927162), patients were randomized between 45 Gy BID in 3 weeks and 66 Gy QD in 33 fractions in 6.6 weeks starting with the second course of chemotherapy [8]. Treatment did not include elective nodal irradiation. The study was designed to investigate whether the higher QD regimen would lead to improved survival. Median overall survival was 30 months for the BID and 25 months for the QD arm. There were no statistically significant differences in the rates of local and metastatic progression. Survival in the control arm (BID) was 12% higher than expected when designing the study, possibly due to improvements in radiotherapy techniques. Based on the study, it can be concluded that a higher dose given QD does not lead to improved survival or better local control. There were no significant differences in acute toxicity, except for more G4 or higher neutropenia in the BID arm (49% vs 38%). The risk of Grade 3-4 oesophagitis was 19% with no significant differences between the two study arms. Based on the results of this trial, 45 Gy given BID in 3 weeks should remain the reference standard. This regimen leads to the best results in the shortest time with the fewest number of fractions. The CONVERT study also indicates that where delivery of a BED scheme is not feasible, a higher dose once-daily schedule does not compromise clinical outcomes. However, it Is surprising that the significantly higher biologically equivalent radiotherapy dose of the QD scheme in the CONVERT study did not translate into better outcome.Does the early distant dissemination of the disease preclude further improvements in local control and survival by local treatment? Or is the influence of the repopulation may greater than calculated in our radiobiological models? The possible benefit of shortened treatment time was evaluated in a phase II study from Norway in which 45 Gy BID in 3 weeks was compared with 42 Gy in 15 fractions in 3 weeks given QD. There was no significant difference in progression free survival at 1 year, the primary endpoint of this study in which 157 patients were enrolled (49% vs 45%). Although overall response rates were similar (88% and 92%), more complete responses were seen in the BID arm (33 vs 13%). In addition, although not statistically significant, overall survival was 25 months for the BID vs 19 months for the QD arm. In the BID scheme, treatment is completed in 3 weeks and a BED10 of 52 Gy is delivered, whereas the same BED10 is reached after about 22 fractions of 2 Gy delivered once-daily. The delivered BED during the last third of the QD treatment does not seem to contribute to outcome. This suggest that repopulation starts very early and that tumor doubling times may be much shorter than generally assumed and a shorter QD scheme may be preferable if treatmenti is not deliverded BID. 1. Fried DB. S J Clin Oncol 2004;22:4837–45. 2. De Ruysscher D.et al., J Clin Oncol 2006;24:1057–63. 3. Pignon JP, et al. N Engl J Med 1992;327:1618–24. 4. Warde P, Payne D. J Clin Oncol 1992;10:890–5. 5. Turrisi AT, ert al. et al. N Engl J Med 1999;340:265–71. 6. Komaki R, et al. Int J Radiat Oncol Biol Phys 2013;85:1082-9. 7. Damhuis R, et al. Clin Oncol 2018;30:17-22. 8. Faivre-Finn C. et al. Lancet Oncol 2017;18:1116-25. 9. Gronberg BH, Acta Oncol 2016;55:591-7. LS-SCLC, SCLC, Radiotherapy

Evaluating the use of prophylactic cranial irradiation in small cell lung cancer.

e18838Background: Intracranial metastases occur in more than 50% of patients with small cell lung cancer (SCLC). Cranial irradiation (PCI) is effective in decreasing the incidence of cerebral metas...

The Road Less Traveled: Should We Omit Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer?

New randomized data from Japan have raised questions regarding the use of prophylactic cranial irradiation for patients with extensive-stage small-cell lung cancer but without detectable brain metastases on magnetic resonance imaging. In the present focused review, we examine the general role of prophylactic cranial irradiation in the management of small-cell lung cancer and present relevant controversies from both sides of the discussion. Future directions for clinical investigation and research are also highlighted. Strategies for neurocognitive protection, including memantine use and hippocampal sparing using modulated radiotherapy techniques, are also presented.