Jutta Kappes

Correlation of Patient-Related Factors and Dose- Volume Histogram Parameters with the Onset of Radiation Pneumonitis in Patients with Small Cell Lung Cancer

Purpose:To analyze the association of patient- and treatment-related factors with the onset of radiation pneumonitis in a homogeneously treated cohort of patients suffering from small cell lung cancer (SCLC).Patients and Methods:242 patients with SCLC staged as limited disease, who had been treated with chemotherapy and three-dimensional conformal radiotherapy, were retrospectively analyzed. Pneumonitis was defined by typical symptoms and radiographic findings and judged clinically relevant, if drug administration and hospitalization were necessary. Patient- (age, gender, smoking history, performance status, tumor localization, benign lung disease) and treatment-related parameters (V10–V40, mean lung dose [MLD]) were analyzed using χ2-tests for categorical parameters and logistic regression for continuous variables.Results:33 patients (13.6%) developed a clinically relevant pneumonitis, of whom three patients died. All cases of pneumonitis developed within 120 days. None of the patient-related parameters correlated significantly with the onset of pneumonitis. Considering treatment-related parameters, a significant correlation of V30 in regard to total lung and V40 in regard to ipsilateral, contralateral and total lung to the risk of pneumonitis was found. So, the estimated risk of a clinically relevant pneumonitis increased from 10% given a V30 of 13% to 30% given a V30 of 35%. In contrast, no significant correlation was found for V10 and V20 and only a trend for MLD.Conclusion:In this series, high-dose radiation volume parameters, i.e., V30 and especially V40, were identified as the most important factors for the development of radiation pneumonitis. Low-dose radiation volume parameters and clinical parameters played an inferior role in predicting the pneumonitis risk.ZusammenfassungZiel:Überprüfung der Assoziation von patienten- und therapiebezogenen Faktoren mit dem Auftreten einer radiogenen Pneumonitis in einem homogen behandelten Patientenkollektiv mit kleinzelligem Bronchialkarzinom (SCLC).Patienten und Methodik:242 Patienten mit SCLC im Stadium „limited disease“, welche mittels Chemotherapie und dreidimensionaler konformaler Radiotherapie behandelt waren, wurden retrospektiv analysiert. Pneumonitis wurde durch das Auftreten typischer Symptome und radiologischer Befunde definiert und als klinisch relevant eingestuft, wenn medikamentöse Behandlung und Klinikeinweisung nötig waren. Patienten- (Alter, Geschlecht, Rauchanamnese, Allgemeinzustand, Tumorlokalisation, gutartige Lungenerkrankung) und behandlungsbezogene Parameter (V10–V40, mittlere Lungendosis [MLD]) wurden mittels χ2-Tests für kategoriale Parameter und logistischer Regression für kontinuierliche Parameter analysiert.Ergebnisse:33 Patienten (13,6%) entwickelten eine klinisch relevante Pneumonitis, drei Patienten starben. Alle Pneumonitisfälle traten innerhalb von 120 Tagen auf. Für keinen der patientenbezogenen Parameter fand sich eine signifikante Korrelation mit dem Auftreten einer Pneumonitis. Hinsichtlich der behandlungsbezogenen Parameter zeigte sich eine signifikante Korrelation der V30 (gesamte Lunge) sowie der V40 (ipsilaterale, kontralaterale oder gesamte Lunge) mit dem Pneumonitisrisiko. So erhöhte sich das geschätzte Risiko einer klinisch relevanten Pneumonitis von 10% bei einer V30 von 13% auf 30% bei einer V30 von 35%. Im Gegensatz hierzu fanden sich keine signifikanten Korrelationen für V10 und V20 und nur ein Trend für die MLD.Schlussfolgerung:Hochdosis-Volumen-Parameter, d.h. V30 und besonders V40, konnten in dieser Serie als wichtigste Faktoren bezüglich der Entwicklung einer radiogenen Pneumonitis identifiziert werden. Niedrigdosis-Volumen-Parameter und klinische Parameter spielten eine untergeordnete Rolle bei der Vorhersage des Pneumonitisrisikos.

Surgery and chemotherapy for small cell lung cancer in stages I-II with or without radiotherapy.

Purpose:To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II.Patients and Methods:39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA–IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy).Results:The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI.Conclusion:Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients.Ziel:Die Effektivität von Operation und anschließender Chemotherapie mit und ohne Strahlentherapie bei der Behandlung von frühen kleinzelligen Bronchialkarzinomen (LSCLC) der Stadien I und II wurde untersucht.Patienten und Methodik:39 Patienten (medianes Alter 62 Jahre) mit LSCLC der Stadien pT1 oder pT2 und pN0 oder pN1 (Stadien IA–IIB) wurden nach Tumoroperation mit systematischer Lymphknotendissektion retrospektiv untersucht. Die mediane Nachbeobachtungszeit betrug 29 Monate. 35 Patienten (90%) erhielten postoperativ median vier Zyklen einer platinhaltigen Chemotherapie. 16 Patienten (41%) erhielten eine adjuvante thorakale Bestrahlung (TRT, median 50 Gy); 21 Patienten (54%) erhielten eine prophylaktische Ganzhirnbestrahlung (PCI, median 30 Gy).Ergebnisse:Das mediane Gesamtüberleben für alle Patienten lag bei 47 Monaten, die 1-, 3- und 5-Jahres-Überlebensraten betrugen 97%, 58% bzw. 49%. Fernmetastasen wurden bei 13 Patienten (33%) nach median 16 Monaten gefunden. Nach adjuvanter TRT wurde ein Trend zugunsten eines verbesserten thorakal-rezidivfreien Überlebens (p = 0,06) sowie eines verbesserten Gesamtüberlebens (p = 0,07) beobachtet. Durch eine PCI wurden das hirnmetastasenfreie Überleben (p = 0,01) und das Gesamtüberleben (p = 0,01) signifikant verbessert.Schlussfolgerung:Eine chirurgische Tumorresektion ist für sorgfältig ausgewählte Patienten sinnvoll. Eine adjuvante Chemotherapie und eine PCI werden für diese Patienten vorgeschlagen. Eine adjuvante TRT wird gegenwärtig bei positivem Lymphknotenstatus (pN1) eingesetzt, da bei diesen Patienten die Wahrscheinlichkeit einer subklinischen Infiltration des mediastinalen lymphatischen Systems höher eingeschätzt wird.

The dynamic pattern of recurrence in curatively resected non-small cell lung cancer patients: Experiences at a single institution

PURPOSE To investigate the hazard function of tumor recurrence in patients with completely (R0) resected non-small cell lung cancer. METHODS A total of 1374 patients treated between 2003 and 2009 with complete resection and systematic lymph node dissection were studied. The risk of recurrence at a given time after operation was studied utilizing the cause-specific hazard function. Recurrence was categorized as local recurrence or distant recurrence. The risk distribution was assessed using clinical and pathological factors. RESULTS The hazard function for recurrence presented an early peak at approximately 10 months after surgery and maintained a tapered plateau-like tail extending up to 8 years. A similar risk pattern was detected for both local recurrence and distant recurrence, while the risk of distant recurrence was higher than that of local recurrence. The double-peaked pattern of hazard rate was present in several subgroups, such as p-stage IA patients. A comparison of histology and status of nodal involvement showed that pN1-2 adenocarcinoma patients demonstrated a high hazard rate of distant recurrence and that pN0 adenocarcinoma patients exhibited a small recurrent risk for a longer time. Squamous cell carcinoma patients showed only little difference in risk. CONCLUSIONS The data may be useful to select patients at high risk of recurrence and may provide information for each patient to decide how to manage the postoperative follow-up individually.

Nine-year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-cell Lung Cancer

Background In 2007, the European Organization for Research and Treatment of Cancer (EORTC) study (ClinicalTrials.gov identifier, NCT00016211) demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) for extensive disease (ED) small‐cell lung cancer (SCLC). Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo magnetic resonance imaging (MRI) of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain MRI findings. Materials and Methods We examined the medical records of 136 patients with ED SCLC who had initially responded to chemotherapy and undergone PCI from 2007 to 2015. The outcomes, radiation toxicity, neurologic progression‐free survival, and OS after PCI were analyzed. Survival and correlations were calculated using log‐rank and univariate Cox proportional hazard ratio analyses. Results The median OS and the median neurologic progression‐free survival after PCI was 12 and 19 months, respectively. No significant survival difference was seen for patients who had undergone MRI before PCI compared with patients who had undergone contrast‐enhanced computed tomography (P = .20). Univariate analysis for OS did not show a statistically significant effect for known cofactors. Conclusion In the present cohort, PCI was associated with improved survival compared with the PCI arm of the EORTC trial, with a nearly doubled median OS period. Also, the median OS was prolonged by 2 months compared with the irradiation arm of the Japanese trial. Micro‐Abstract In 2007, a European Organization for Research and Treatment of Cancer (EORTC) study demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) in extensive disease small‐cell lung cancer. Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo imaging of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain magnetic resonance imaging findings. Of our patients, 87% underwent brain imaging before PCI. In the present retrospective analysis, we found that PCI leads to a nearly doubled median OS compared with the irradiation arm of the EORTC trial, with a 2‐month prolonged median OS compared with the irradiation arm of the Japanese trial.

Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation

OBJECTIVES Patients with brain metastases from small-cell lung cancer (SCLC) who underwent prior prophylactic cranial irradiation (PCI) are often treated with a second course of whole brain radiation therapy (Re-WBRT) or stereotactic radiosurgery (SRS) for purposes of palliation in symptomatic patients, hope for increased life expectancy or even as an alternative to untolerated steroids. Up to date there is only limited data available regarding the effect of this treatment. This study examines outcomes in patients in a single institution who underwent cerebral re-irradiation after prior PCI. METHODS We examined the medical records of 76 patients with brain metastases who had initially received PCI between 2008 and 2015 and were subsequently irradiated with a second course of cerebral radiotherapy. Patients underwent re-irradiation using either Re-WBRT (88%) or SRS (17%). The outcomes, including symptom palliation, radiation toxicity, and overall survival (OS) following re-irradiation were analyzed. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. Treatment-related toxicity was classified according to CTCAE v4.0. RESULTS Median OS of all patients was 3 months (range 0-12 months). Median OS after Re-WBRT was 3 months (range 0-12 months). Median OS after SRS was 5 months (range 0-12 months). Karnofsky performance status scale (KPS ≥50%) was significantly associated with improved OS in both univariate (HR 2772; p=0,009) and multivariate analyses (HR 2613; p=0,024) for patients receiving Re-WBRT. No unexpected toxicity was observed and the observed toxicity remained consistently low. Symptom palliation was achieved in 40% of symptomatic patients. CONCLUSIONS In conclusion, cerebral re-irradiation after prior PCI is beneficial for symptom palliation and is associated with minimal side effects in patients with SCLC. Our survival data suggests that it is primarily useful in patients with adequate performance status.

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

&NA; The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT (BMS‐score). The new BMS score was more prognostic than the RPA and ds‐GPA score. BMS score and RPA showed the most significant differences between classes. Introduction: Patients with small‐cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT. Patients and Methods: The present study was conducted utilizing a single‐institution, previously described, retrospective database of patients with SCLC who were treated with WBRT (n = 221). Univariate and multivariate analyses were performed to generate the “brain metastases from SCLC score” (BMS score) based on favorable prognostic factors: Karnofsky performance status (KPS > 70), extracerebral disease status (stable disease/controlled), and time of appearance of BM (synchronous). Furthermore, the disease‐specific graded prognostic assessment score as well as the recursive partitioning analysis (RPA) were performed and compared with the new BMS score by using the log‐rank (Mantel‐Cox) test. Results: BMS score and RPA showed the most significant differences between classes (P < .001). BMS score revealed a mean overall survival (OS) of 2.62 months in group I (0‐1 points), 6.61 months in group II (2‐3 points), and 12.31 months in group III (4 points). The BMS score also identified the group with the shortest survival (2.62 months in group I), and the numbers of patients in each group were most equally distributed with the BMS score. Conclusion: The new BMS score was more prognostic than the RPA and disease‐specific graded prognostic assessment scores. The BMS score is easy to use and reflects known prognostic factors in contemporary patients with SCLC treated with WBRT. Future studies are necessary to validate these findings.

Outcome and prognostic factors of postoperative radiation therapy (PORT) after incomplete resection of non-small cell lung cancer (NSCLC)

PURPOSE Current guidelines recommend postoperative radiation therapy (PORT) for incompletely resected non-small cell lung cancer (NSCLC). However, there is still a paucity of evidence for this approach. Hence, we analyzed survival in 78 patients following radiotherapy for incompletely resected NSCLC (R1) and investigated prognostic factors. PATIENTS AND METHODS All 78 patients with incompletely resected NSCLC (R1) received PORT between December 2001 and September 2014. The median total dose for PORT was 60 Gy (range 44-68 Gy). The majority of patients had locally advanced tumor stages (stage IIA (2.6%), stage IIB (19.2%), stage IIIA (57.7%) and stage IIIB (20.5%)). 21 patients (25%) received postoperative chemotherapy. RESULTS Median follow-up after radiotherapy was 17.7 months. Three-year overall (OS), progression-free (PFS), local (LPFS) and distant progression-free survival (DPFS) rates were 34.1, 29.1, 44.9 and 51.9%, respectively. OS was significantly prolonged at lower nodal status (pN0/1) and following dose-escalated PORT with total radiation doses >54 Gy (p=0.012, p=0.013). Furthermore, radiation doses >54 Gy significantly improved PFS, LPFS and DPFS (p=0.005; p=0.050, p=0.022). Interestingly, survival was neither significantly influenced by R1 localization nor by extent (localized vs. diffuse). Multivariate analyses revealed lower nodal status and radiation doses >54.0 Gy as the only independent prognostic factors for OS (p=0.021, p=0.036). CONCLUSION For incompletely resected NSCLC, PORT is used for improving local tumor control. Local progression is still the major pattern of failure. Radiation doses >54 Gy seem to support improved local control and were associated with better OS in this retrospective study.

Brustwandtumor — immer ein Tumorrezidiv?

Bei einem Patienten wurde fünf Monate nach Operation und adjuvanter Chemotherapie eines NSCLC eine Raumforderung der Thoraxwand mit ossärer Destruktion der Rippen und pulmonalen Rundherden festgestellt. Wie wichtig eine aktuelle histologische Sicherung ist, zeigt der Fallbericht.

Parenchymal and Functional Lung Changes after Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer—Experiences from a Single Institution

Introduction This study aimed to evaluate parenchymal and functional lung changes following stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) patients and to correlate radiological and functional findings with patient and treatment characteristics as well as survival. Materials and methods Seventy patients with early-stage NSCLC treated with SBRT from 2004 to 2015 with more than 1 year of CT follow-up scans were analyzed. Incidence, morphology, severity of acute and late lung abnormalities as well as pulmonary function changes were evaluated and correlated with outcome. Results Median follow-up time was 32.2 months with 2-year overall survival (OS) of 83% and local progression-free survival of 88%, respectively. Regarding parenchymal changes, most patients only developed mild to moderate CT abnormalities. Mean ipsilateral lung dose (MLD) in biological effective dose and planning target volume size were significantly associated with maximum severity score of parenchymal changes (p = 0.014, p < 0.001). Furthermore, both maximum severity score and MLD were significantly connected with OS in univariate analysis (p = 0.043, p = 0.025). For functional lung changes, we detected significantly reduced total lung capacity, forced expiratory volume in 1 s, and forced vital capacity (FVC) parameters after SBRT (p ≤ 0.001). Multivariate analyses revealed SBRT with an MLD ≥ 9.72 Gy and FVC reduction ≥0.54 L as independent prognostic factors for inferior OS (p = 0.029, p = 0.004). Conclusion SBRT was generally tolerated well with only mild toxicity. For evaluating the possible prognostic impact of MLD and FVC reduction on survival detected in this analysis, larger prospective studies are truly needed.