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1.
J Radiat Res ; 64(5): 850-856, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37658697

ABSTRACT

This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78 Gy in 39 fractions to the prostate and 46.8 Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85-108) months. The median age was 72 (IQR = 67-75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6-56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.


Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Male , Humans , Aged , Androgen Antagonists , Retrospective Studies , Prostatic Neoplasms/radiotherapy , Pelvis
2.
Cancer Diagn Progn ; 2(6): 648-653, 2022.
Article in English | MEDLINE | ID: mdl-36340451

ABSTRACT

BACKGROUND/AIM: To evaluate whether whole-pelvis (WP) volumetric modulated arc therapy (VMAT) is associated with increased late toxicity compared with prostate-only (PO) VMAT in patients with localized prostate cancer. PATIENTS AND METHODS: Participants comprised 384 consecutive patients treated with definitive VMAT to 78 Gy in 39 fractions from July 2011 to August 2016. Of these, 183 patients received PO-VMAT and 201 patients received initial WP-VMAT to 46.8 Gy in 26 fractions using a simultaneous integrated boost technique. Gastrointestinal (GI) and genitourinary (GU) toxicities were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Median follow-up was 49 months (range=16-88 months) in the PO-VMAT group and 52 months (range=10-85 months) in the WP-VMAT group. Frequencies of Grade 3 late GI and GU toxicities were ≤3% across both groups. No patients experienced Grade 4+ toxicity. Cumulative incidences of Grade 2+ late GI and GU toxicities were similar between PO- and WP-VMAT groups (p=0.508 and p=0.838, respectively). Five-year cumulative incidences of Grade 2+ late GI and GU toxicities were 12.2% and 6.6% for the PO-VMAT group and 12.3% and 8.9% for the WP-VMAT group, respectively. CONCLUSION: WP-VMAT did not increase late GI and GU toxicities. This suggests that concerns about increasing toxicity profile are insufficient reason for omitting WPRT for patients with high-risk prostate cancer.

3.
Pract Radiat Oncol ; 8(2): e49-e55, 2018.
Article in English | MEDLINE | ID: mdl-29310978

ABSTRACT

PURPOSE: This study aimed to compare bowel and urinary health-related quality of life (HRQOL) between prostate-only (PO) volumetric modulated arc therapy (VMAT) and whole-pelvis (WP) VMAT in patients with localized prostate cancer. METHODS AND MATERIALS: A total of 234 patients treated with definitive VMAT to 78 Gy in 39 fractions were enrolled. Of these, 108 patients received PO-VMAT and 126 patients received initial WP-VMAT to 46.8 Gy in 26 fractions using a simultaneous integrated boost technique. HRQOL was prospectively assessed before radiation therapy (baseline), and 3, 6, 12, and 24 months after treatment using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: Baseline HRQOL scores did not differ significantly between the 2 groups. No significant between-group differences in HRQOL change from baseline were observed for all bowel and urinary EPIC domains. The proportion of patients showing a clinically relevant decrease in bowel and urinary HRQOL scores from baseline was similar between the groups throughout the follow-up period. An analysis of individual HRQOL items showed that patients undergoing WP-VMAT were more likely to report moderate/big problems with bloody stools (P = .039) and overall bowel problems (P = .008) than those undergoing PO-VMAT at 12 months. There was no significant between-group difference in any individual items at 24 months, however. CONCLUSIONS: Bowel and urinary HRQOL is largely similar for patients receiving PO-VMAT and WP-VMAT during 24 months of follow-up, with the only differences seen in responses to specific bowel HRQOL items at 12 months.


Subject(s)
Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/psychology , Quality of Life , Radiotherapy Dosage
4.
J Contemp Brachytherapy ; 9(6): 499-507, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29441093

ABSTRACT

PURPOSE: To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h) and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR) brachytherapy for localized prostate cancer. MATERIAL AND METHODS: Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 (125I) brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ), posterior-superior (PSQ), anterior-inferior (AIQ), and posterior-inferior (PIQ). Predictive factors and cut-off values of biochemical failure-free survival (BFFS) and toxicities of LDR brachytherapy were analyzed. RESULTS: The median follow-up time was 69.5 months. Seven patients (5.4%) had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D90 (the minimal dose received by 90% of the volume) of PSQ and PIQ at 24 h, and D90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D90 were 145 Gy at 24 h and 160 Gy at 1 month. D90 of the whole prostate was not significant at 24 h and at 1 month. D90 of PSQ at 1 month was a significant factor for rectal hemorrhage. CONCLUSIONS: Post-implant D90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D90 of PSQ at 1 month is also a significant factor for rectal hemorrhage.

5.
Pract Radiat Oncol ; 6(6): 395-401, 2016.
Article in English | MEDLINE | ID: mdl-27374192

ABSTRACT

PURPOSE: To investigate optimal bladder volumes at treatment planning (TP) in prostate cancer patients who undergo volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: To determine the minimum value, 122 patients were classified into 6 groups according to the bladder volume at TP: <100 mL (group 1), 100-149 mL (group 2), 150-199 mL (group 3), 200-249 mL (group 4), 250-299 mL (group 5), and ≥300 mL (group 6). Bladder volumes receiving more than 70 Gy (V70Gy) and V50Gy were calculated in each subgroup and compared with the bladder dose-volume constraints specified in our institution. To determine the maximum value, 64 patients who underwent uniform nursing interventions were classified into the same 6 groups. Bladder volumes on cone beam computed tomography (CBCT) images were measured once weekly during treatment, for a total of 8 measurements. Relative bladder volumes (bladder volume on CBCT image [mL]/bladder volume at TP [mL] × 100%) were evaluated in each of the 6 subgroups. RESULTS: The upper bounds of the 95% confidence intervals of the mean V70Gy and V50Gy values in group 1 exceeded the dose constraints at our institution. The mean relative bladder volumes were 104%, 91%, 77%, 81%, 63%, and 59% in groups 1, 2, 3, 4, 5, and 6, respectively. The institutional criterion of 70% for the mean relative bladder volume was achieved in groups 1-4, but it could not be achieved in groups 5-6. Therefore, the patients in groups 2-4 met both institutional dose constraints for the bladder at TP and the institutional criterion for the mean relative bladder volume during treatment. CONCLUSIONS: The optimal bladder volumes at TP were between 100 and 250 mL in this setting. Nursing intervention needs to be implemented before treatment planning to ensure that patients achieve the optimal bladder volume range.


Subject(s)
Organs at Risk/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Urinary Bladder/diagnostic imaging , Aged , Aged, 80 and over , Cone-Beam Computed Tomography , Humans , Male , Middle Aged , Organ Size , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
6.
Br J Radiol ; 89(1063): 20150945, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27164029

ABSTRACT

OBJECTIVE: The purpose of this study was to retrospectively evaluate the effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification in patients who received three-dimensional conformal radiotherapy (3D CRT) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) by analyzing toxicity and prognostic factors. METHODS: 56 consecutive patients who had locally advanced HCC with PVTT treated by 3D CRT between September 2007 and April 2013 were retrospectively reviewed. RESULTS: The median survival time of all patients was 6.4 months. Receiver-operating characteristic (ROC) analysis identified MELD score = 7.5 [area under the curve (AUC) 0.81] and Child-Pugh score = 6.5 (AUC 0.86) as the best cut-off values for predicting the incidence of complications over Common Terminology Criteria for Adverse Events grade 2. There was no significant difference in the discrimination power between the MELD score and the Child-Pugh score on comparison of the two ROC curves (p = 0.17). On multivariate analysis, age, MELD score and radiotherapy dose were significant prognostic factors for overall survival (p = 0.021, 0.038 and 0.006, respectively). In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis. CONCLUSION: This study showed that the best MELD score cut-off value is 7.5 and that the MELD score is a better prognostic factor than the Child-Pugh classification in 3D CRT for HCC with PVTT. ADVANCES IN KNOWLEDGE: The MELD score is useful for predicting the risk of severe toxicities and the prognosis of patients treated with 3D CRT for PVTT.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , End Stage Liver Disease/radiotherapy , Liver Neoplasms/radiotherapy , Portal Vein/pathology , Radiotherapy, Conformal/methods , Venous Thrombosis/radiotherapy , Aged , Area Under Curve , Carcinoma, Hepatocellular/complications , End Stage Liver Disease/complications , Female , Humans , Liver Neoplasms/complications , Male , Prognosis , ROC Curve , Retrospective Studies , Survival Analysis , Venous Thrombosis/complications
7.
J Radiat Res ; 57(3): 273-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26951076

ABSTRACT

The purpose of this study was to determine appropriate beam arrangement for volumetric-modulated arc therapy (VMAT)-based stereotactic body radiation therapy (SBRT) in the treatment of patients with centrally located lung tumors. Fifteen consecutive patients with centrally located lung tumors treated at our institution were enrolled. For each patient, three VMAT plans were generated using two coplanar partial arcs (CP VMAT), two non-coplanar partial arcs (NCP VMAT), and one coplanar full arc (Full VMAT). All plans were designed to deliver 70 Gy in 10 fractions. Target coverage and sparing of organs at risk (OARs) were compared across techniques. PTV coverage was almost identical for all approaches. The whole lung V10Gy was significantly lower with CP VMAT plans than with NCP VMAT plans, whereas no significant differences in the mean lung dose, V5Gy, V20Gy or V40Gy were observed. Full VMAT increased mean contralateral lung V5Gy by 12.57% and 9.15% when compared with NCP VMAT and CP VMAT, respectively. Although NCP VMAT plans best achieved the dose-volume constraints for mediastinal OARs, the absolute differences in dose were small when compared with CP VMAT. These results suggest that partial-arc VMAT may be preferable to minimize unnecessary exposure to the contralateral lung, and use of NCP VMAT should be considered when the dose-volume constraints are not achieved by CP VMAT.


Subject(s)
Lung Neoplasms/radiotherapy , Radiosurgery/methods , Radiotherapy, Intensity-Modulated/methods , Aged , Aged, 80 and over , Humans , Lung Neoplasms/diagnostic imaging , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Tomography, X-Ray Computed
8.
Br J Radiol ; 89(1062): 20150930, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26959612

ABSTRACT

OBJECTIVE: To compare dosimetric parameters and acute toxicity rates between whole-pelvic (WP) and prostate-only (PO) volumetric-modulated arc therapy (VMAT) in patients with localized prostate cancer. METHODS: A total of 224 consecutive patients treated with definitive VMAT to 78 Gy in 39 fractions were enrolled. Of these, 119 patients received initial WP VMAT at 46.8 Gy in 26 fractions using a simultaneous integrated boost technique, and 105 patients received PO VMAT. Image-guided radiotherapy was practised with daily cone beam CT. RESULTS: The mean rectal dose, the rectal volume receiving ≥30 Gy (V30Gy), rectal V50Gy, the mean bladder dose, bladder V30Gy and bladder V50Gy were significantly increased in the WP group (p < 0.05 each); however, the rectal V70Gy did not differ between groups (p = 0.101), and the bladder V70Gy was significantly lower in the WP group (p = 0.029). The WP group experienced a significantly increased frequency of acute grade 2 diarrhoea relative to the PO group (5.9% vs 0%; p = 0.015). No differences were seen between the WP and PO groups in terms of acute grade 2 proctitis (10.1% vs 6.7%; p = 0.360) and genitourinary (GU) toxicity (12.6% vs 10.5%; p = 0.620). CONCLUSION: Despite larger rectum and bladder volumes at low- and medium-dose levels, WP VMAT resulted in no significant increase in acute proctitis or GU toxicity when compared with PO VMAT. ADVANCES IN KNOWLEDGE: This study demonstrates that whole-pelvic radiotherapy has comparable acute toxicity to those observed with prostate-only radiotherapy when VMAT with daily image guidance is used.


Subject(s)
Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiation Exposure/statistics & numerical data , Radiation Injuries/epidemiology , Radiotherapy, Image-Guided/statistics & numerical data , Radiotherapy, Intensity-Modulated/statistics & numerical data , Aged , Humans , Japan/epidemiology , Male , Middle Aged , Organ Sparing Treatments/statistics & numerical data , Pelvis/radiation effects , Prevalence , Prostatic Neoplasms/epidemiology , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Risk Factors , Treatment Outcome
9.
J Radiat Res ; 56(1): 141-50, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25304328

ABSTRACT

The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose-volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients.


Subject(s)
Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/radiotherapy , Radiation Injuries/epidemiology , Radiotherapy Planning, Computer-Assisted/methods , Aged , Comorbidity , Humans , Japan/epidemiology , Male , Middle Aged , Organ Sparing Treatments/methods , Organ Sparing Treatments/statistics & numerical data , Organs at Risk/radiation effects , Pelvis , Prevalence , Radiation Injuries/etiology , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated , Risk Factors , Treatment Outcome
10.
ScientificWorldJournal ; 2013: 289809, 2013.
Article in English | MEDLINE | ID: mdl-23401667

ABSTRACT

We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)--ERGO++, Monaco, or Pinnacle--and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3 ± 17.7, 149.7 ± 8.4, and 185.8 ± 15.6 MU/min and 132.7 ± 8.4, 217.6 ± 13.1, and 127.5 ± 27.1 sec. During a follow-up period of 486.2 ± 289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (P < 0.0001), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (P < 0.0001). Each TPS was successfully used for prostate VMAT planning without significant differences in early clinical outcomes despite significant TPS-specific delivery parameter variations.


Subject(s)
Prostate/radiation effects , Prostatic Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Femur/radiation effects , Gastrointestinal Hemorrhage/etiology , Hematuria/etiology , Humans , Male , Neoplasm Staging , Organs at Risk , Prostate/pathology , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Rectum/radiation effects , Treatment Outcome , Urinary Bladder/radiation effects
11.
J Radiat Res ; 54(4): 697-705, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-23418389

ABSTRACT

We created volumetric-modulated arc therapy (VMAT) plans for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma, and compared the results with those from three-dimensional conformal radiotherapy (3D-CRT) and rotational conformal radiotherapy (R-CRT) plans. CT scan data from 10 consecutive patients with PVTT treated with 3D-CRT between January 2008 and January 2010 were utilized in the analysis. We analyzed the dosimetric properties of the plans for the 10 patients using the three different techniques with three different isocenter doses of 50, 56 and 60 Gy in 2-Gy fractions. The D95, Dmean, homogeneity index and conformity index were compared for the planning target volume (PTV). The Dmean, V20 and V30 were also compared for normal livers. The monitor units (MUs) and the treatment time were also evaluated. The normal liver V30 for VMAT was significantly less than that for 3D-CRT for the prescribed doses of 56 and 60 Gy (P < 0.05). It was also found that the normal liver V30 resulting from 3D-CRT was prohibitively increased when the prescribed dose was increased in two steps. For PTV D95, we found no significant differences between the three techniques for the 50- and 56-Gy prescriptions, or between VMAT and the other techniques for the 60-Gy prescription. The differences in the MUs and treatment times were not statistically significant between VMAT and 3D-CRT. We have demonstrated that VMAT may be a more advantageous technique for dose escalation reaching 60 Gy in the treatment of PVTT due to the reduced normal liver V30.


Subject(s)
Carcinoma, Hepatocellular/complications , Liver Neoplasms/complications , Portal Vein/pathology , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/methods , Aged , Female , Humans , Liver/radiation effects , Male , Middle Aged , Movement , Portal Vein/diagnostic imaging , Radiometry/methods , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Thrombosis/radiotherapy , Time Factors , Tomography, X-Ray Computed/methods
12.
Chem Commun (Camb) ; 47(41): 11531-3, 2011 Nov 07.
Article in English | MEDLINE | ID: mdl-21952312

ABSTRACT

The sunlight-induced photocatalytic oxidation of aqueous benzene on TiO(2)-supported gold nanoparticles was considerably improved when the reaction was conducted under a CO(2) atmosphere. 13% yield and 89% selectivity of phenol was obtained on P25-supported gold nanoparticles under 230 kPa of CO(2).


Subject(s)
Benzene/chemistry , Carbon Dioxide/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Phenol/chemical synthesis , Titanium/chemistry , Air , Benzene/radiation effects , Catalysis , Oxidation-Reduction , Photochemistry , Sunlight , Water/chemistry
13.
Jpn J Radiol ; 28(1): 43-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20112092

ABSTRACT

PURPOSE: The aim of this study was to update data of radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer, a retrospective study was conducted. MATERIALS AND METHODS: Results of early concurrent chemoradiotherapy with accelerated hyperfractionation in 30 patients between 1998 and 2005 were retrospectively reviewed. The prescribed dose was 45 Gy in 30 fractions in all patients. RESULTS: All patients received a full dose of radiation therapy; however, interruptions for >or=5 days, mainly due to hematologic toxicity, were required in 18 patients (60%). The 5-year Kaplan-Meier survival rate and the median survival time were 26% and 26 months, respectively. The 4-year in-field control rate was 56%. Sites of relapse were local relapse in 9 patients (6 for in-field relapse, 3 for marginal relapse) and distant metastases in 16 patients (11 for distant metastases only, 5 for distant metastases with local relapse). The sites of marginal relapse were the upper margin in two patients and the peripheral margin in one patient. Grade 3 radiation esophagitis was observed in only three patients. CONCLUSION: Because in-field control was insufficient, a more effective approach should be sought to provide better local control.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Neoplasms/therapy , Neoplasm Recurrence, Local/pathology , Neoplasms, Second Primary/pathology , Radiotherapy, Computer-Assisted/methods , Small Cell Lung Carcinoma/therapy , Chemotherapy, Adjuvant/methods , Combined Modality Therapy/methods , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Male , Neoplasm Staging , Radiotherapy Dosage , Retrospective Studies , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/secondary , Treatment Failure
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