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Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer

Primary Purpose

Small-cell Lung Cancer, SCLC, Small Cell Lung Cancer Limited Stage

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hippocampal-sparing Prophylactic Cranial Irradiation
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small-cell Lung Cancer focused on measuring Prophylactic Cranial Irradiation, PCI, Hippocampal-sparing irradiation

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient must have newly diagnosed and confirmed small-cell lung cancer (SCLC)
  • Patient must have a performance status of 1 or higher
  • Patients must not have received previous irradiation to the brain
  • Patients must have limited stage disease with complete response to chemotherapy and consolidative chest radiotherapy that was documented at least on standard chest x-rays within one month of study entry
  • Negative MRI or CT scan of the brain at least one month before protocol entry
  • Women of child-bearing potential must have a negative pregnancy test and also agree to use adequate contraceptives while on protocol
  • Patient must be able to understand and sign the informed consent document
  • Patient must be informed of the investigational aspect to this trial prior to singing the informed consent document

Exclusion Criteria:

  • Patients receiving prior external beam irradiation to the head or neck, including any form of stereotactic irradiation
  • Radiographic evidence of brain metastases and/or ipsilateral lung metastases/malignant pleural effusion
  • Planned concurrent chemotherapy or antitumoral agent during PCI
  • Concomitant malignancy or malignancy within the past five years other than nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • Patients with minimal pleural effusion evident on chest X-ray; minimal pleural effusion visible on chest CT is allowed.
  • Patients with epilepsy requiring permanent oral medication
  • Patients must not have a serious medical or psychiatric illness that would, in the opinion of the investigator, prevent informed consent or completion of protocol treatment, and/or follow-up visits.
  • Patients may not take Memantine. This is the only eligibility criterion that has been added to those of RTOG 0212, since some physicians might now prescribe Memantine. This medication would not have been given at the time of enrollment on RTOG 0212 and its administration could confound the results of this study.

Sites / Locations

  • Bayview Medical Center
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hippocampal-sparing PCI

Arm Description

Hippocampal-sparing PCI 25 Gy in 10 fractions

Outcomes

Primary Outcome Measures

Effect of Hippocampal-sparing Prophylactic Cranial Irradiation (PCI) on Possible Delayed Recall Toxicity as Assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R) for Delayed Recall
The primary endpoint of this study is cognitive function or memory. Memory is measured by participant performance on the Hopkins Verbal Learning Test-Revised for delayed recall (HVLT-R-Delayed Recall) at 6 months following hippocampal-sparing PCI. The HVLT-Delayed minimum and Maximum scores are 0-12. A higher score means a better outcome.

Secondary Outcome Measures

Compare Cognitive Function Following Sparing PCI to That of Standard PCI
Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall (0-36) higher = better Delayed Recall (0-12) higher = better Discrimination (-12 to 12) higher = better Trail Making A & B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) Letter Word Fluency (0-120) higher = better Category Word Fluency (0-120) higher = better Verbal Fluency (0-240) higher = better Learning and Memory Verbal Composite T score (mean = 100, standard deviation = 15), higher = better Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Compare Cognitive Function Following Sparing PCI to That of Standard PCI
Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall (0-36) higher = better Delayed Recall (0-12) higher = better Discrimination (-12 to 12) higher = better Trail Making A & B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) Letter Word Fluency (0-120) higher = better Category Word Fluency (0-120) higher = better Verbal Fluency (0-240) higher = better Learning and Memory Verbal Composite T score (mean = 100, standard deviation = 15), higher = better Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Compare Cognitive Function Following Sparing PCI to That of Standard PCI
Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall (0-36) higher = better Delayed Recall (0-12) higher = better Discrimination (-12 to 12) higher = better Trail Making A & B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) Letter Word Fluency (0-120) higher = better Category Word Fluency (0-120) higher = better Verbal Fluency (0-240) higher = better Learning and Memory Verbal Composite T score (mean = 100, standard deviation = 15), higher = better Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire (QLQ)-C30
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 6 months and baseline. Questions on the Quality of Life Questionnaire (QLQ-C30) assessment are on a four-point scale from "not at all" to "very much". Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. Questions on the QLQ-C30 cover the following: Dyspnoea Insomnia Appetite Constipation Diarrhoea Finances Fatigue Nausea/Vomiting Pain Physical Function Role Function Emotional Function Cognitive Function Social Function Global QoL
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment QLQ-C30
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 12 months and baseline. Questions on the Quality of Life Questionnaire (QLQ-C30) assessment are on a four-point scale from "not at all" to "very much". Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. Questions on the QLQ-C30 cover the following: Dyspnoea Insomnia Appetite Constipation Diarrhoea Finances Fatigue Nausea/Vomiting Pain Physical Function Role Function Emotional Function Cognitive Function Social Function Global QoL
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire-Brain Cancer (QLQ-BN20)
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 6 months and baseline. Questions on the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20) are rated on a four-point scale ('not at all', 'a little', 'quite a bit' and 'very much'), and are linearly transformed to a 0-100 scale. Higher scores represent more severe symptoms. Questions on the QLQ-BN20 cover the following: Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Visual Disorder Motor Dysfunction Communication Deficit
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Using the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20).
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 12 months and baseline. Questions on the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20) are rated on a four-point scale ('not at all', 'a little', 'quite a bit' and 'very much'), and are linearly transformed to a 0-100 scale. Higher scores represent more severe symptoms. Questions on the QLQ-BN20 cover the following: Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Visual Disorder Motor Dysfunction Communication Deficit Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Scale Visual Disorder Scale Motor Dysfunction Scale Communication Deficit Scale
Number Participants With Hippocampus Brain Metastases Following Sparing PCI
The number of participants with brain metastases after sparing PCI treatment was assessed to be compared to two existing studies.
Assess if Development of Leptomeningeal Carcinomatosis Following Sparing PCI is Higher Than Expected
Determine whether development of leptomeningeal carcinomatosis following hippocampal-sparing PCI is higher than expected.
Percentage of Participants Surviving Following Hippocampal-sparing PCI
To evaluate the survival rates of study participants following hippocampal-sparing PCI.

Full Information

First Posted
November 30, 2012
Last Updated
September 22, 2021
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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1. Study Identification

Unique Protocol Identification Number
NCT01797159
Brief Title
Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer
Official Title
"A Phase II Trial of Hippocampal-Sparing Cranial Irradiation (PCI) for Small-Cell Lung Cancer (SCLC)"
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
March 11, 2013 (Actual)
Primary Completion Date
March 18, 2018 (Actual)
Study Completion Date
March 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The Investigators are looking to compare standard treatment for the management of small cell lung cancer (SCLC) which is prophylactic cranial Irradiation (PCI) (shown to be very good in patient survival) with cranial sparing PCI. Although standard of care PCI is successful in patient survival it also has neurologic side-effects. The Investigators are hoping the cranial sparing PCI has the same positive survival results with the added benefit of lowering neurological side-effects.
Detailed Description
The standard of care in management of small cell lung cancer consists of chemotherapy plus thoracic radiation followed by prophylactic cranial irradiation (PCI) based on a randomized trial that demonstrated a significant improvement in overall survival (OS) with PCI. Unfortunately radiation therapy to the brain is associated with neurocognitive toxicity, which may be at least in part related to radiation induced injury to neural progenitor cells in the hippocampus. Both human and animal data suggest an inverse relationship between radiation dose to the hippocampus and performance on neuropsychological testing. We hypothesize that hippocampal sparing PCI will allow improved performance on tests of short term memory and executive function compared to a historical control (RTOG 0212) receiving the same dose of conventional PCI. The primary objective of this study is to evaluate performance on the Hopkins Verbal Learning Test-Revised for delayed recall at 6 months following hippocampal-sparing PCI relative to the historical control. Secondary objectives are to estimate: 1) composite cognitive function following hippocampal-sparing PCI relative to the historical control and 2) the rate of metastases in the hippocampus at 2 years following hippocampal-sparing PCI. The long term goal of this research is to reduce the long term sequelae of radiation therapy for both primary and metastatic brain tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small-cell Lung Cancer, SCLC, Small Cell Lung Cancer Limited Stage
Keywords
Prophylactic Cranial Irradiation, PCI, Hippocampal-sparing irradiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hippocampal-sparing PCI
Arm Type
Experimental
Arm Description
Hippocampal-sparing PCI 25 Gy in 10 fractions
Intervention Type
Radiation
Intervention Name(s)
Hippocampal-sparing Prophylactic Cranial Irradiation
Intervention Description
Hippocampal-sparing Prophylactic Cranial Irradiation
Primary Outcome Measure Information:
Title
Effect of Hippocampal-sparing Prophylactic Cranial Irradiation (PCI) on Possible Delayed Recall Toxicity as Assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R) for Delayed Recall
Description
The primary endpoint of this study is cognitive function or memory. Memory is measured by participant performance on the Hopkins Verbal Learning Test-Revised for delayed recall (HVLT-R-Delayed Recall) at 6 months following hippocampal-sparing PCI. The HVLT-Delayed minimum and Maximum scores are 0-12. A higher score means a better outcome.
Time Frame
Baseline, 6 months and 12 months post radiation treatment
Secondary Outcome Measure Information:
Title
Compare Cognitive Function Following Sparing PCI to That of Standard PCI
Description
Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall (0-36) higher = better Delayed Recall (0-12) higher = better Discrimination (-12 to 12) higher = better Trail Making A & B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) Letter Word Fluency (0-120) higher = better Category Word Fluency (0-120) higher = better Verbal Fluency (0-240) higher = better Learning and Memory Verbal Composite T score (mean = 100, standard deviation = 15), higher = better Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Time Frame
Baseline
Title
Compare Cognitive Function Following Sparing PCI to That of Standard PCI
Description
Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall (0-36) higher = better Delayed Recall (0-12) higher = better Discrimination (-12 to 12) higher = better Trail Making A & B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) Letter Word Fluency (0-120) higher = better Category Word Fluency (0-120) higher = better Verbal Fluency (0-240) higher = better Learning and Memory Verbal Composite T score (mean = 100, standard deviation = 15), higher = better Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Time Frame
6 months post radiation treatment
Title
Compare Cognitive Function Following Sparing PCI to That of Standard PCI
Description
Composite cognitive function following hippocampal-sparing PCI relative to a historical control receiving standard PCI. HVLT-R Hopkins Verbal Learning Test Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall (0-36) higher = better Delayed Recall (0-12) higher = better Discrimination (-12 to 12) higher = better Trail Making A & B (0-300 seconds) higher = poorer Controlled Oral Word Association (COWA) (0-180) higher = better Mini-Mental State Exam (MMSE) (0-30) higher = better Perceptual Comparison Test (PCT) (0-128) higher = better Brief Test of Attention (BTA) (0-20) higher = better Calibrated Ideational Fluency Assessment (CIFA) Letter Word Fluency (0-120) higher = better Category Word Fluency (0-120) higher = better Verbal Fluency (0-240) higher = better Learning and Memory Verbal Composite T score (mean = 100, standard deviation = 15), higher = better Visual Composite T score (mean = 100, standard deviation = 15), higher = better
Time Frame
12 months post radiation treatment
Title
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire (QLQ)-C30
Description
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 6 months and baseline. Questions on the Quality of Life Questionnaire (QLQ-C30) assessment are on a four-point scale from "not at all" to "very much". Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. Questions on the QLQ-C30 cover the following: Dyspnoea Insomnia Appetite Constipation Diarrhoea Finances Fatigue Nausea/Vomiting Pain Physical Function Role Function Emotional Function Cognitive Function Social Function Global QoL
Time Frame
Baseline and 6 months post radiation treatment
Title
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment QLQ-C30
Description
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 12 months and baseline. Questions on the Quality of Life Questionnaire (QLQ-C30) assessment are on a four-point scale from "not at all" to "very much". Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. Questions on the QLQ-C30 cover the following: Dyspnoea Insomnia Appetite Constipation Diarrhoea Finances Fatigue Nausea/Vomiting Pain Physical Function Role Function Emotional Function Cognitive Function Social Function Global QoL
Time Frame
Baseline and 12 months post radiation treatment
Title
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Quality of Life Questionnaire-Brain Cancer (QLQ-BN20)
Description
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 6 months and baseline. Questions on the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20) are rated on a four-point scale ('not at all', 'a little', 'quite a bit' and 'very much'), and are linearly transformed to a 0-100 scale. Higher scores represent more severe symptoms. Questions on the QLQ-BN20 cover the following: Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Visual Disorder Motor Dysfunction Communication Deficit
Time Frame
Baseline and 6 months post radiation treatment
Title
Compare Change in Quality of Life of Hippocampal-sparing PCI Treatment Outcome to Standard PCI Treatment Using the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20).
Description
Evaluate quality of life following hippocampal-sparing PCI relative to historical control receiving standard PCI. Difference between 12 months and baseline. Questions on the Quality of Life Questionnaire-Brain Cancer (QLQ-BN20) are rated on a four-point scale ('not at all', 'a little', 'quite a bit' and 'very much'), and are linearly transformed to a 0-100 scale. Higher scores represent more severe symptoms. Questions on the QLQ-BN20 cover the following: Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Visual Disorder Motor Dysfunction Communication Deficit Headaches Seizures Drowsy Hair loss Itching Weakness Bladder Future Uncertainty Scale Visual Disorder Scale Motor Dysfunction Scale Communication Deficit Scale
Time Frame
Baseline and 12 months post radiation treatment
Title
Number Participants With Hippocampus Brain Metastases Following Sparing PCI
Description
The number of participants with brain metastases after sparing PCI treatment was assessed to be compared to two existing studies.
Time Frame
12 months
Title
Assess if Development of Leptomeningeal Carcinomatosis Following Sparing PCI is Higher Than Expected
Description
Determine whether development of leptomeningeal carcinomatosis following hippocampal-sparing PCI is higher than expected.
Time Frame
6 months, 12 months, 18 months and 24 months post radiation treatment
Title
Percentage of Participants Surviving Following Hippocampal-sparing PCI
Description
To evaluate the survival rates of study participants following hippocampal-sparing PCI.
Time Frame
Up to 24 months post radiation treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must have newly diagnosed and confirmed small-cell lung cancer (SCLC) Patient must have a performance status of 1 or higher Patients must not have received previous irradiation to the brain Patients must have limited stage disease with complete response to chemotherapy and consolidative chest radiotherapy that was documented at least on standard chest x-rays within one month of study entry Negative MRI or CT scan of the brain at least one month before protocol entry Women of child-bearing potential must have a negative pregnancy test and also agree to use adequate contraceptives while on protocol Patient must be able to understand and sign the informed consent document Patient must be informed of the investigational aspect to this trial prior to singing the informed consent document Exclusion Criteria: Patients receiving prior external beam irradiation to the head or neck, including any form of stereotactic irradiation Radiographic evidence of brain metastases and/or ipsilateral lung metastases/malignant pleural effusion Planned concurrent chemotherapy or antitumoral agent during PCI Concomitant malignancy or malignancy within the past five years other than nonmelanomatous skin cancer or carcinoma in situ of the cervix Patients with minimal pleural effusion evident on chest X-ray; minimal pleural effusion visible on chest CT is allowed. Patients with epilepsy requiring permanent oral medication Patients must not have a serious medical or psychiatric illness that would, in the opinion of the investigator, prevent informed consent or completion of protocol treatment, and/or follow-up visits. Patients may not take Memantine. This is the only eligibility criterion that has been added to those of RTOG 0212, since some physicians might now prescribe Memantine. This medication would not have been given at the time of enrollment on RTOG 0212 and its administration could confound the results of this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Redmond, M.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21227
Country
United States
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share data with PIs who are not included on the study team.
Citations:
PubMed Identifier
28581401
Citation
Redmond KJ, Hales RK, Anderson-Keightly H, Zhou XC, Kummerlowe M, Sair HI, Duhon M, Kleinberg L, Rosner GL, Vannorsdall T. Prospective Study of Hippocampal-Sparing Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2017 Jul 1;98(3):603-611. doi: 10.1016/j.ijrobp.2017.03.009. Epub 2017 Mar 14.
Results Reference
derived

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Hippocampal Prophylactic Cranial Irradiation for Small Cell Lung Cancer

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