Gunther Klautke

Postoperative Chemotherapy May Not Be Necessary for Patients With ypN0-Category After Neoadjuvant Chemoradiotherapy of Rectal Cancer

PurposeAfter neoadjuvant radiochemotherapy and surgery, there is no general agreement about whether postoperative chemotherapy is necessary. With the help of clinical and pathohistologic data, prognostic factors were determined as a basis for the decision to spare a patient additional chemotherapy or to urgently recommend it.ResultsNinety-five patients treated with neoadjuvant 5-fluorouracil-based radiochemotherapy (November 4, 1997 and June 15, 2004) without distant metastases and an R0 (microscopically complete) resection were evaluated. Adjuvant chemotherapy (5-fluorouracil or 5-fluorouracil/folinic acid) was given to 65 of 95 patients (68.4 percent). The disease-free survival rate after 36 months was chosen as the target parameter (median follow-up, 36 months).MethodsThe five-year survival rate for all patients was 80.3 ± 5.6 percent; the five-year disease-free survival was 78.1 ± 5.1 percent; the five-year local control rate was 94.2 ± 5.1 percent. In the univariate and multivariate analysis of the disease-free survival, the pathohistologic lymph node status after radiochemotherapy (ypN) was the only significant prognostic parameter. Disease-free survival (36 months) for patients without lymph node metastases (ypN0) was excellent, independent of whether they had received postoperative chemotherapy (n = 43; 87.5 ± 6.0 percent) or not (n = 29; 87.7 ± 6.7 percent). Patients with ypN2 status have, despite chemotherapy, a poor disease-free survival at 30 ± 17.6 percent after 36 months.ConclusionsThese retrospective data suggest that, for some patients, postoperative chemotherapy can be spared. For patients with ypN2 status, an intensification of the postoperative chemotherapy should be considered. Further evaluation in prospective studies is urgently recommended.

6-Year Experience of Concurrent Radiochemotherapy with Vinorelbine Plus a Platinum Compound in Multimorbid or Aged Patients with Inoperable Non-Small Cell Lung Cancer

Background and Purpose:Although poor-risk patients represent no minority in inoperable non-small cell lung cancer (NSCLC), there is little experience with concurrent radiochemotherapy (RCT) in this group. Here, the authors report on the feasibility and efficacy of RCT with vinorelbine plus carboplatin or cisplatin in NSCLC patients with comorbidities and poor general health or advanced age.Patients and Methods:A total of 66 patients (ten women, 56 men, median age 68 years) with inoperable NSCLC and an increased risk of treatment side effects (WHO performance score of 2–3; cardiac, pulmonary or renal failure or extensive weight loss before treatment, or an age of 71–78 years) were treated with vinorelbine 12.5 mg/m2 on days 1, 8, 15, 29, 36, and 43 in combination with either carboplatin 70 mg/m2 (n = 59) or cisplatin 20 mg/m2 (n = 7) on days 1–5 and 29–33 in addition to receiving conventional fractionated radiotherapy with doses of up to 63 Gy (90% isodose).Results:62 of 66 patients (94%) reached the 90% level of the prescribed radiation dose, and 41/66 patient (62%) received at least two cycles of the platinum compound and four cycles of vinorelbine. The following hematologic side effects (CTC classification [Common Toxicity Criteria]) were observed: grade 3 (12%) and grade 4 (15%) thrombocytopenia, grade 3 (38%) and grade 4 (4%) leukocytopenia, and anemia requiring transfusion (26%). Other side effects (CTC) included grade 3 (3%) and grade 4 (2%) esophagitis and grade 3 pneumonitis (3%). The response rates were as follows: complete remission 18%, partial remission 56%, stable disease 21%, and progressive disease 5%. The cumulative survival rates were 53%, 24%, and 8% at 12 months, 24 months, and 5 years, respectively.Conclusion:After including a larger group of patients than in 2003 and following the patients for several years, the authors determine that concurrent RCT consisting of vinorelbine plus a platinum compound and conventional fractionated radiotherapy can be carried out with manageable toxicity, even in this negatively selected population of patients. Their survival rates were comparable to those achieved in other studies with simultaneous RCT.Hintergrund und Ziel:Obwohl Patienten mit erhöhten Behandlungsrisiken keine Minderheit in der Gruppe der inoperablen nichtkleinzelligen Bronchialkarzinome (NSCLC) darstellen, sind die Erfahrungen mit einer simultanen Radiochemotherapie (RCT) gering. Die Autoren berichten über die Durchführbarkeit und Effektivität der RCT mit Vinorelbin und Carboplatin oder Cisplatin bei komorbiden Patienten in reduziertem Allgemeinzustand oder fortgeschrittenem Alter.Patienten und Methodik:Insgesamt wurden 66 Patienten (zehn Frauen, 56 Männer, medianes Alter 68 Jahre) mit inoperablem NSCLC und erhöhten Behandlungsrisiken (WHO-Performance-Score 2/3; kardialer, pulmonaler oder renaler Insuffizienz oder ausgeprägtem prätherapeutischem Gewichtsverlust oder in einem Alter von 71–78 Jahren) mit Vinorelbin 12,5 mg/m2 an den Tagen 1, 8, 15, 29, 36 und 43 und Carboplatin 70 mg/m2 (n = 59) oder Cisplatin 20 mg/m2 (n = 7) d1–5 und 29–33 sowie einer konventionell fraktionierten Radiotherapie bis 63 Gy (90%-Isodose) behandelt.Ergebnisse:62 von 66 Patienten (94%) erreichten ein Dosislevel von 90% der zu applizierenden Strahlendosis, 41/66 Patienten (62%) erhielten mindestens zwei Kurse des Platinderivats und vier Kurse Vinorelbin. Folgende hämatologische Nebenwirkungen (CTC-Klassifikation [Common Toxicity Criteria]) wurden beobachtet: Thrombozytopenie Grad 3 (12%) und Grad 4 (15%), Leukozytopenie Grad 3 (38%) und Grad 4 (4%) sowie transfusionsbedürftige Anämie (26%). Andere Nebenwirkungen bestanden aus Ösophagitiden Grad 3 (3%) und Grad 4 (2%) sowie Pneumonitis Grad 3 (3%). Die Ansprechraten waren wie folgt: komplette Remission 18%, partielle Remission 56%, stabile Erkrankung 21% und Krankheitsprogression 5%. Das kumulative Überleben betrug nach 12 Monaten 53%, nach 24 Monaten 24% und nach 5 Jahren 8%.Schlussfolgerung:Auch nach Einschluss einer größeren Patientengruppe als 2003 und nach einer langen Nachbeobachtungszeit wird eine simultane RCT mit Vinorelbin und einem Platinderivat sowie einer konventionell fraktionierten Radiotherapie mit einer beherrschbaren Toxizität bei diesem negativ selektionierten Patientengut für durchführbar erachtet. Die Überlebensdaten erreichen die in anderen Studien durch eine simultane RCT erzielten Ergebnisse.

Neoadjuvant Radiochemotherapy in Locally Advanced Gastric Carcinoma

Background and Purpose:Gastric carcinoma is characterized by a high rate of local recurrences and distant metastases and is often not resectable due to locally advanced stage. The aim of this study was to examine feasibility and effectiveness of neoadjuvant radiochemotherapy (RCT) for locally advanced, primarily nonresectable gastric carcinoma and to achieve curative resection.Patients and Methods:21 patients with locally advanced gastric cancer located in cardia (n = 17) and corpus (n = 4; seven cT3; 14 cT4; 18 cN+; all cM0) with a median age of 61 years were scheduled to receive neoadjuvant RCT. Therapy consisted of a conventionally fractionated, conformal radiotherapy using the shrinking-field technique (1.8 Gy to 45 Gy + 5.4 Gy) and chemotherapy using cisplatin (20 mg/m2, d1–5, 29–33), 5-fluorouracil (5-FU; 800 mg/m2, d1–5, 29–33) or paclitaxel (135 mg/m2, d1, 29). 4–6 weeks after completion of RCT, surgery was performed whenever feasible.Results:Hematologic toxicity was moderate with grade 3 leukopenia in 10/21 patients and grade 3 thrombopenia in 5/21 (CTC). Nonhematologic toxicities consisted of 5/21 cases of fever as well as one fungal sepsis. Following RCT, tumors were classified resectable in 16/21 patients (76%); 12/21 patients (58%) were operated on, 11/12 achieved clear margins (R0). Response was as follows: complete remission (CR) 3/21 (14%), partial remission 13/21 (62%), no change 3/21 (14%), systemic progressive disease (PD) 2/21 (10%). The median survival and the 2-year survival rates were 18 months and 42%, respectively, for the patients following R0 resections as compared to 10 months and 0% for the remaining patients (p = 0.035). Local control (4 years) for patients following R0 resection was 89%.Conclusion:Neoadjuvant RCT is feasible and locally highly effective but must be further investigated involving a higher number of patients.Hintergrund und Ziel:Das Magenkarzinom ist durch eine hohe Rate an Lokalrezidiven und Fernmetastasen gekennzeichnet und im lokal fortgeschrittenen Stadium oftmals irresektabel. Ziel dieser Studie war die Überprüfung der Durchführbarkeit und Effektivität einer neoadjuvanten Radiochemotherapie (RCT) beim lokal fortgeschrittenen, primär nicht resektablen Magenkarzinom mit dem Ziel, die Resektabilität zu erreichen.Patienten und Methodik:21 Patienten mit lokal fortgeschrittenen Kardia- (n = 17) und Korpuskarzinomen (n = 4) des Magens (sieben cT3; 14 cT4; 18 cN+; alle cM0) im Alter von median 61 Jahren wurden zur neoadjuvanten RCT vorgestellt. Die Therapie bestand aus einer konventionell fraktionierten, konformalen Strahlentherapie in Shrinking-Field-Technik (1,8 Gy bis 45 Gy + 5,4 Gy) und einer cisplatinhaltigen (20 mg/m2, d1–5, 29–33) Chemotherapie mit 5-Fluorouracil (5-FU; 800 mg/m2, d1–5, 29–33) oder Paclitaxel (135 mg/m2, d1, 29). 4–6 Wochen nach Abschluss der RCT erfolgte die Operation.Ergebnisse:Die Hämatotoxizität war mit Leukopenien Grad 3 bei 10/21 Patienten und Thrombopenien Grad 3 nach CTC bei 5/21 Patienten moderat; nichthämatologische Toxizitäten waren in 5/21 Fällen Fieber sowie eine Pilzsepsis. Nach der RCT wurden die Tumoren bei 16/21 Patienten (76%) als resektabel eingestuft; 12/21 Patienten (58%) wurden operiert, 11/12 wurden R0-reseziert. Die Ansprechraten waren wie folgt: komplette Remission (CR) 3/21 (14%), partielle Remission (PR) 13/21 (62%), stabile Erkrankung (NC) 3/21 (14%), systemische Progression (PD) 2/21 (10%). Das mediane Überleben und die 2-Jahres-Überlebensrate betrugen nach R0-Resektion 18 Monate und 42% im Vergleich zu 10 Monaten und 0% bei den übrigen Patienten (p = 0,035). Die lokale Kontrolle (4 Jahre) nach R0-Resektion lag bei 89%.Schlussfolgerung:Die neoadjuvante Radiochemotherapie ist durchführbar und lokal hocheffektiv, muss aber an größeren Patientenzahlen weiter überprüft werden.

Prevalence of Brain Metastases Immediately before Prophylactic Cranial Irradiation in Limited Disease Small Cell Lung Cancer Patients with Complete Remission to Chemoradiotherapy: A Single Institution Experience

This single-center study investigated the prevalence of brain metastases immediately before prophylactic cranial irradiation in 40 consecutive limited disease small cell lung cancer complete responders to chemoradiotherapy and revealed that 13/40 (32.5%; 95% confidence interval: 18–47%) patients suffer relapse with brain metastases and show a significantly worse prognosis than those without detected brain metastases.

Total and Single Doses Influence the Effectiveness of Radiotherapy in Palliative Treatment of Plasmacytoma

Purpose:In a retrospective analysis of radiotherapy of plasmacytomas, the effectiveness and the prognostic factors in regard to pain reduction and recalcification were evaluated.Patients and Methods:138 patients (70 women, 68 men; 15–86 years, median 61 years) were irradiated at 272 target volumes (TVs) from January 1970 to December 2003.Results:In 192/225 TVs (85.3%), there was a pain reduction. The recalcification rate was 44.7% (51/114 TVs). Significant parameters for pain relief in the multivariate analysis were completeness of therapy (odds ratio [OR] 87.8; p < 0.001 vs. interruption), patients < 60 years (OR 23.0; p < 0.001 vs. ≥ 70 years), and a single dose of 2 Gy (OR 11.0; p = 0.027 vs. 4–15.0 Gy). Significant parameters for recalcification in the multivariate analysis were concurrent chemotherapy (OR 12.3; p < 0.001 vs. no chemotherapy), no fractures in the TV (OR 5.9; p < 0.004 vs. fracture), and a dose of 40–< 50 Gy (OR 21.9; p = 0.035 vs. < 30 Gy) or ≥ 50 Gy (OR 26.4; p = 0.033 vs. < 30 Gy)Conclusion:Radiotherapy is a very effective palliative treatment. Patients with a reduced general condition, with multiple bone lesions and a poor prognosis profit from short-term schemes (e.g., 1 × 8 Gy to 10 × 3 Gy). Patients in good general condition with a life expectancy of > 1 year and an osteolysis at risk of fracture, should be treated with doses up to 40–50 Gy (20–25 × 2 Gy), in order to achieve the best possible recalcification and pain relief.Ziel:In einer retrospektiven Analyse bei Plasmozytomen wurde die Wirksamkeit der Strahlentherapie hinsichtlich der Schmerzreduktion und Rekalzifizierung untersucht.Patienten und Methodik:138 Patienten (70 Frauen, 68 Männer, 15–86 Jahre, medianes Alter 61 Jahre) wurden mit 272 Zielvolumina von Januar 1970 bis Dezember 2003 behandelt.Ergebnisse:Bei 192/225 Zielvolumina (85,3%) konnte eine Schmerzreduktion erzielt werden. Eine Rekalzifikation ließ sich bei 51/114 Zielvolumina (44,7%) erreichen. Signifikante Parameter für eine Schmerzreduktion waren multivariat eine vollständig durchgeführte Strahlentherapie (Odds-Ratio [OR] 87,8; p < 0,001 vs. Unterbrechung), ein Alter < 60 Jahre (OR 23,0; p < 0,001 vs. ≥ 70 Jahre), und eine Einzeldosis von 2 Gy (OR 11,0; p = 0,027 vs. 4–15,0 Gy). Die Rekalzifikation wurde multivariat beeinflusst durch eine simultane Radiochemotherapie (OR 12,3; p < 0,001 vs. keine Chemotherapie), keine Fraktur im Zielvolumen (OR 5,9; p < 0,004 vs. Fraktur) und eine Summendosis von 40–< 50 Gy (OR 21,9; p = 0,035 vs. < 30 Gy) oder ≥ 50 Gy (OR 26,4; p = 0,033 vs. < 30 Gy).Schlussfolgerung:Die Strahlentherapie ist eine sehr effektive palliative Behandlung. Patienten in einem reduzierten Allgemeinzustand, mit multiplen Osteolysen und einer schlechten Prognose profitieren von kurzen Schemata (1 × 8 Gy bis 10 × 3 Gy). Demgegenüber profitieren Patienten mit einer Lebenserwartung von > 1 Jahr von Dosierungen von 40–50 Gy (Einzeldosis 2 Gy), da damit eine gute Rekalzifizierung und Schmerzlinderung erreicht werden können.

Radiotherapy in Pancreatic Cancer

Purpose and Approach:To summarize the current knowledge on the role of radiotherapy in the treatment of pancreatic ductal adenocarcinoma (PDAC). The results of meta-analyses, phase III-studies, and phase II-studies using chemoradiation (CRT) and chemotherapy for resectable and non-resectable PDAC are reviewed.Results and Conclusion:The role of CRT is undefined in the adjuvant setting but there may be a role as additive treatment after R1 resection. Locally advanced borderline resectable tumors may shrink down and be subject to potentially curative resections. In locally advanced clearly unresectable cancers the effect of CRT as well as chemotherapy is poorly defined and the sequence of chemotherapy and CRT should be re-evaluated. Patients with PDAC should always be treated within studies to identify optimal treatment results.Ziel und Vorgehen:Zusammenfassung des derzeitigen Wissens über die Rolle der Radiotherapie für die Behandlung des duktalen Adenokarzinoms des Pankreas (PDAC). Die Ergebnisse von Metaanalysen, Phase-III- und Phase-II-Studien mit Radiochemotherapie und Chemotherapie werden für Patienten mit resektablem und irresektablem PDAC dargestellt.Ergebnisse und Schlussfolgerung:Im adjuvanten Ansatz ist die Rolle der Radiochemotherapie nicht definiert, jedoch ist eine Rolle als additive Therapie in der R1-Situation möglich. Lokal fortgeschrittene, borderline-resektable Tumoren können verkleinert werden und dann potentiell kurativen Resektionen zugänglich gemacht werden. Für lokal fortgeschrittene, eindeutig irresektable Tumoren ist der Effekt der Radiochemotherapie wie der Chemotherapie schlecht definiert and die Abfolge von Radiochemotherapie und Chemotherapie sollte neu untersucht werden. Patienten mit PDAC sollten immer im Rahmen von Studien behandelt werden, um optimale Behandlungsergebnisse zu identifizieren.

Significance of Radiation Therapy for Adenocarcinomas of the Esophagus, Gastroesophageal Junction and Gastric Cancer with Special Reference to the MAGIC Trial

Strahlenther Onkol 2007;183:163–9 DOI 10.1007/s00066-007-7702-7 Introduction Radiation therapy plays an important role in the treatment of squamous cell carcinomas of the esophagus, and is used in both the definitive treatment situation and the neoadjuvant approach [23]. On the other hand, in the subgroup of adenocarcinomas of the esophagus or tumors of the gastroesophageal junction and stomach, the clinical value of irradiation remains a contentious issue. Surgical resection still plays the decisive role in the treatment of these tumor entities. Randomized studies like the MAGIC trial [17] and the SWOG trial [48] have given new impetus to the debate on the value of chemotherapy and radiotherapy in these patients. The objective of this editorial is to elucidate the current role of radiotherapy in the treatment of adenocarcinomas of the esophagus and stomach from a radiooncologic perspective.

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors

Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced head and neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a very aggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionated-accelerated radiotherapy. The final results of the phase II study are listed below.For the phase II trial 32 patients (29 male, 3 female) with histologically diagnosed locally advanced non-metastatic squamous cell carcinoma of the head and neck in stage III/IV were treated from 1999 to 2003. Radiotherapy was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. The chemotherapy regime included administering cisplatinum on d 1–5 and on d 29–33 at doses of 20 mg/m2 and during the entire course of treatment paclitaxel was administered twice a week at doses of 25 mg/m2.The 5-yr overall and disease-free survival rates were 48% and 43%. Twenty-two (69%) patients reached a clinically complete response and 8 (25%) a partial response (for two of the patients the response rate is not known). Two (6%) patients died during the treatment. Seven (22%) patients developed local recurrences and six of these patients have in the meantime died. With regards to the four (12%) patients who developed distant metastases, three of them have in the meantime died and two (6%) patients have died as a result of secondary malignancies.Seven out of 25 (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients developed grade 3 mucositis. No cases of grade 4 mucositis were observed; however, one patient out of 25 (4%) was classified with grade 4 dermatitis. One out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22 patients (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a grade 3 leukopenia, and 2 out of 25 patients (8%) experienced a grade 4 eutropenic infection. Dysphagia was a significant late toxicity. Out of 24 patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a grade 3 xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients.

Combined Treatment Modality in Small Cell Lung Cancer

Introduction Small cell lung cancer (SCLC) is extremely sensitive to both chemotherapy and radiation. Nonetheless, the employment of irradiation to treat SCLC has become a rather contentious issue in the last years. Radiotherapy has been an integral part of treatment of limited-stage SCLC since the early 1990s; in these patients, radiotherapy was normally administered sequentially, after completion of chemotherapy. In the case of extensive-stage disease, radiotherapy was not considered to be indicated except in patients with existing or imminent complications. The last 5 years have seen a shift in the indications for and timing of radiotherapy, yet the optional method of fractionation is still unclear. The objective of this review is to discuss the recent developments in the use of radiotherapy for treatment of SCLC and to discuss their possible implications for daily practice.

Tumour regression and mesorectal lymph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum

Neoadjuvant radiation or chemoradiation is currently the treatment of choice for patients with locally advanced carcinoma of the rectum. To assess the effects of chemoradiation on tumour regression and on uninvolved mesorectal lymph nodes, a consecutive series of 76 patients receiving neoadjuvant chemoradiation and a stage‐adapted control series of 57 patients without pretreatment were studied. Densities of cells positive for CD4 (T‐helper cells), CD8 (cytotoxic T‐cells), CD83 (mature dendritic cells), and CD57 (natural killer cells) were determined on immunostains. Tumour regression was graded, and presence or absence of extramural tumour was recorded. The densities of CD4+ T‐lymphocytes and CD83+ dendritic cells in the paracortex of mesorectal lymph nodes were observed to be significantly reduced, as were the densities of CD57+ cells in the follicles; densities of CD8+ T‐lymphocytes did not differ. Strong, moderate and poor tumour regression was observed in 29, 25, and 22 cases, respectively. For 12 patients, absence of extramural vital or regressing tumour was recorded, indicating pretherapeutic overstaging. The results bring to mind that neoadjuvant chemoradiation as a side effect may have a negative impact on anti‐tumour immunity. Together with the drawback of overstaging the results argue for a careful selection of patients.