Thomas Schnabel

Usefulness of Tumor Volumetry as a Prognostic Factor of Survival in Head and Neck Cancer

Background: The TNM classification system of tumor stage does not always reflect the actual tumor mass present at diagnosis. This study aimed at evaluating the prognostic value of volumetric data regarding survival in head and neck cancer patients being treated with either cisplatin or carboplatin administered concomitantly with radiotherapy. Patients and Methods: We retrospectively analyzed 107 patients suffering from squamous cell carcinoma of the head and neck in a Greek-German cooperational study (see Table 1). All patients were treated by radiotherapy and concomitant chemotherapy. 65 patients received chemotherapy with carboplatin and 42 with cisplatin. More than 6,200 CT scans were analyzed by digitalization of contours which subsequently led to the computation of the tumor volume (primary and macroscopic lymph node metastases). Results: Median follow-up was 43 months and median survival 30 months. Median initial tumor volume was 32.5 ml (range 2.1–220.1 ml) in the carboplatin and 44.4 ml (range 3.2–202.5 ml) in the cisplatin group (see Figure 1). After treatment, tumor volumes did not differ significantly (median of 3.1 ml [range 0.0–167.1 ml] and 3.5 ml [range 0.0–166.0 ml], respectively). 41 patients (63.1%) died in the carboplatin group and 22 patients (52.4%) in the cisplatin group (see Figure 2). Pretherapeutic tumor volume was prognostic with respect to survival while TNM classification and age were not. Pretherapeutic tumor volume was negatively and percent decrease in tumor volume positively associated with survival (see Tables 2 and 3). Conclusion: Knowledge of the initial tumor volume adds valuable information in terms of prognosis. Initial tumor volume should be included in all future clinical trials regarding head and neck cancer patients.Hintergrund: Das TNM-Tumorklassifikationssystem repräsentiert nicht immer die tatsächliche Tumormasse bei Diagnose. Diese Studie hatte die Überprüfung der prognostischen Wertigkeit volumetrischer Analysen bezüglich des Überlebens bei Patienten mit Kopf-Hals-Tumoren, die radiotherapeutisch und mit begleitender Chemotherapie (Cisplatin oder Carboplatin) behandelt wurden, zur Zielsetzung. Patienten und Methodik: Wir analysierten retrospektiv 107 Patienten mit Kopf-Hals-Tumoren im Rahmen einer griechisch-deutschen Kooperationsstudie (s. Tabelle 1). Alle Patienten erhielten eine Radiotherapie, 65 Patienten zusätzlich eine Carboplatin-, 42 Patienten eine Cisplatin-Chemotherapie. Mehr als 6 200 CT-Bilder wurden mittels Digitalisierung der Konturen bearbeitet, sodass daraus das Tumorvolumen (Primarius inkl. makroskopischer Lymphknotenmetastasen) berechnet werden konnte. Ergebnisse: Das mediane Follow-up betrug 43 Monate, das mediane Überleben 30 Monate. Das mediane initiale Tumorvolumen betrug 32,5 ml (2,1–220,1 ml) in der Carboplatin- und 44,4 ml (3,2–202,5 ml) in der Cisplatin-Gruppe (s. Abbildung 1). Nach Beendigung der Therapie unterschieden sich die Tumorvolumina nicht signifikant (Median von 3,1 ml [0,0–167,1 ml] bzw. 3,5 ml [0,0–166,0 ml]). In der Carboplatin-Gruppe starben 41 (63,1%) der Patienten, in der Cisplatin-Gruppe 22 (52,4%) (s. Abbildung 2). Das prätherapeutische Tumorvolumen war im Gegensatz zur TNM-Klassifikation prognostisch bezüglich des Überlebens. Das prätherapeutische Tumorvolumen war negativ, die prozentuale Abnahme des Tumorvolumens positiv mit dem Überleben assoziiert (s. Tabellen 2 und 3). Schlussfolgerung: Das initiale Tumorvolumen ist ein wichtiger Prognostikator des Überlebens und sollte in alle zukünftigen Studien bezüglich Kopf-Hals-Tumoren inkludiert werden.

Reirradiation for Recurrent Neck Metastases of Head-and-Neck Tumors Using CT-Guided Interstitial 192Ir HDR Brachytherapy

Purpose:To report the therapeutic results obtained with CT-guided interstitial high-dose-rate brachytherapy (HDR-BRT) as exclusive treatment for recurrent neck metastases of head-and-neck tumors.Patients and Methods:Between 1995 and 1999, 49 patients with prior radiation therapy (RT) with or without surgery for primary head-and-neck tumors were treated for recurrent neck metastases located within previously irradiated volumes. All patients had fixed lymphadenopathy with a mean tumor volume of 96 cm3 (range, 15–452 cm3). There were 38 males and eleven females with a mean age of 60 years (range, 28–79 years). All patients had previously received RT as primary or adjuvant treatment with a mean dose of 54 Gy (range, 45–80 Gy). 36 patients (73%) underwent surgery, and 26 (53%) received adjuvant or palliative chemotherapy. The accelerated hyperfractionated interstitial HDR-BRT (2 × 3.0 Gy/day) delivered 30 Gy in 37/49 (75%) and 36 Gy in 12/49 implants (25%).Results:At a minimum 6-week follow-up, the response rate was 83% (41/49) with complete remission in 20% (10/49) and partial remission in 63% (31/49) of the implanted tumor sites. 8/49 patients (17%) did not respond to the treatment. After 19 months of median follow-up, the local control rate was 69% and a total of 15/49 patients (30%) experienced local disease progression. Of these, nine (18%) had locoregional progression and six (12%) progression within the treated volume. The median post-BRT survival was 14 months. The overall survival rate was 52% at 1 year, 31% at 2 years, and 6% at 3 years.Conclusion:In patients with recurrent cervical lymphadenopathy of head-and-neck tumors, exclusive interstitial HDR-BRT can provide palliation and tumor control.Ziel:Vorstellung der CT-gestützten interstitiellen High-Dose-Rate-Brachytherapie (HDR-BRT) als ausschließliches Therapieverfahren in der Behandlung zervikaler Lymphknotenrezidive von Kopf-Hals-Tumoren.Patienten und Methodik:Zwischen 1995 und 1999 wurden insgesamt 49 Patienten mit zervikalen Lymphknotenrezidiven behandelt. Alle 49 Patienten (38 männlich, elf weiblich, Durchschnittsalter 60 Jahre [28–79 Jahre]) waren mit einer durchschnittlichen Zielvolumendosis von 54 Gy (45–80 Gy) vorbestrahlt, und 36 (73%) waren voroperiert. Eine adjuvante oder palliative Chemotherapie war bei 26 Patienten (53%) durchgeführt worden. Alle Patienten erhielten eine akzeleriert-hyperfraktionierte BRT (2 × 3 Gy/Tag) bis zu einer Gesamtdosis von 30 Gy in 37/49 (75%) und 36 Gy in 12/49 Implantaten (25%). Das durchschnittliche Tumorvolumen betrug 96 cm3 (15–452 cm3).Ergebnisse:Die Ansprechrate nach 6 Wochen betrug 83%. Bei 10/49 Patienten (20%) wurde eine komplette Remission, bei 31/49 (63%) eine partielle Remission erzielt. 8/49 (17%) zeigten kein Ansprechen bzw. eine lokale Progredienz. Nach einer medianen Nachbeobachtungszeit von 19 Monaten betrug die lokale Kontrollrate 69%, bei 15/49 Patienten (30%) lag ein Tumorprogress vor. Dabei zeigten 9/15 (60%) eine lokoregionäre Progression. Lediglich bei 6/15 (40%) handelte es sich um echte In-loco-Rezidive, die innerhalb des BRT-Volumens gelegen waren. Das mediane Überleben betrug 14 Monate, die Gesamtüberlebensrate nach 1 Jahr 52%, nach 2 Jahren 31% und nach 3 Jahren 6%.Schlussfolgerung:Die CT-gestützte interstitielle HDR-BRT ist ein wertvolles Instrument für die palliative Behandlung von Patienten mit Halslymphknotenrezidiven bei Kopf-Hals-Tumoren.

Simultaneous Radiotherapy and Chemotherapy with Carboplatin in Inoperable Squamous Cell Carcinoma of the Head and Neck: A Phase II Study

Fifty-six untreated patients with inoperable squamous cell carcinoma of the head and neck were treated with carboplatin 70 mg/m2 i.v. daily on days 1-5 and 29-33 in combination with simultaneous conventional radiation up to a target volume dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons, 21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two courses of carboplatin. Patients who showed pCR after surgery received no further radiotherapy. In all other patients radiotherapy was continued using a shrinking field technique up to a target absorbed dose of 70-74 Gy. Combined modality induced 66% complete remission (CR) and an overall response rate of 98%. After completion of the whole treatment program (combined modality +/- surgery) 53 (94%) of the 56 patients were disease free. The median survival for all patients is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression was the most frequent toxicity, but rarely was severe; leukopenia and thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and ototoxicity were not seen. The addition of carboplatin did not increase the rate of surgical complication over that expected for preoperative radiotherapy. Two patients died of pulmonary embolism after surgery. Combined modality with carboplatin and simultaneous radiation is a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck.

Effect of recombinant human granulocyte colony stimulating factor (r-metHuG-CSF) as an adjunct to large-field radiotherapy: A phase I study

PURPOSE To test the feasibility of recombinant human granulocyte colony stimulating factor application during large-field radiotherapy. METHODS AND MATERIALS Fifteen patients with clinically and histologically proven malignancy who received large-field radiotherapy entered this study. Administration of recombinant granulocyte colony stimulating factor (G-CSF) at a dose of 300 microgram subcutaneously was started on Friday and was continued on Saturday and Sunday after the first radiotherapy treatment, which began on the Monday before. In this way four courses of G-CSF were applied every Friday, Saturday, and Sunday during the radiotherapy period. Absolute neutrophil cell (ANC) and blood counts were monitored twice a week and compared to a second group of 15 patients who received large-field radiotherapy without G-CSF. Before and at the end of every cycle of G-CSF, ANC, blood counts, and biochemistry were measured. We compared the myelotoxicity of the patients treated with G-CSF with 15 patients without G-CSF treated at the same period with large-field radiotherapy, in match pair technique. RESULTS G-CSF increased the ANC throughout the period of irradiation, and the treatment time needed for competing radiotherapy was shorter in the group who received G-CSF. Fourteen of 15 patients who received G-CSF treatment completed large-field radiotherapy without pause. Only 1 of 15 patients not receiving G-CSF was able to receive radiation treatment on schedule. Patients receiving G-CSF completed treatment with the mantle-field technique in 24 days and those with the abdominal bath technique in 26.5 days. Conversely, patients treated without G-CSF completed treatment with the mantle-field technique in 30.5 days and those with the abdominal bath technique in 36 days. The most frequent side effect was musculoskeletal pain. CONCLUSION The prophylactic application of G-CSF during large-field radiotherapy before the onset of neutropenia was feasible in this schedule. Whether or not this shortening of treatment duration will translate into an improvement in efficacy is not clear.

Präoperative Bestrahlung mit interstitiellem Radiohyperthermie-Boost bei Mammatumoren ≥3 cm

AIM The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. PATIENTS AND METHODS One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy 192Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 x 2 Gy/week. Local hyperthermia with 43.5-44.5 degrees C over 60 minutes was delivered immediately before interstitial radiotherapy. RESULTS One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases. CONCLUSION In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.ZusammenfassungHintergrundUntersucht wurde die Brusterhaltungsrate mit und ohne Myokutanlappenunterstützung nach präoperativer Chemotherapie, Radiotherapie und Hyperthermie.Patienten und Methode158 Patientinnen im Stadium IIA-IV wurden präoperativ mit Chemotherapic, Radiotherapie und Hyperthermie behandelt. Die Radiotherapie bestand aus einem primären interstitiellen Boost des palpablen Tumors von 10 Gy192Ir-HDR-Afterloading-Therapie sowie einer perkutanen Brustbestrahlung von 50 Gy in einer Fraktionierung von 5 × 2 Gy pro Woche. Die Hyperthermiebehandlung mit 43,5 bis 44,5 °C über 60 Minuten erfolgte unmittelbar vor der interstitiellen Bestrahlung.ErgebnisseEs wurden insgesamt 142 Patientinnen einer Sanierungsoperation unterzogen. 74 Patientinnen (52%) wurden brusterhaltend operiert. In 53 Fällen (37%) wurden Myokutanlappen verwendet. Nach einer medianen Beobachtungszeit von 20 Monaten entwickelte eine Patientin ein isoliertes Thoraxwandrezidiv. 14 weitere lokoregionäre Rezidive traten in Kombination mit Fernmetastasen auf.SchlußfolgerungNach der vorgestellten präoperativen Behandlung wurde in mehr als der Hälfte der Fälle die Brust erhalten. Die niedrige isolierte Lokalrezidivrate von 0,6% (1/158) nach 20 Monaten muß durch längere Nachbeobachtung validiert werden.AbstractAimThe aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia.Patients and MethodsOne hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy192Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 × 2 Gy/week. Local hyperthermia with 43.5–44.5°C over 60 minutes was delivered immediately before interstitial radiotherapy.ResultsOne hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases.ConclusionIn about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.

Long-Term Effects on the Intelligence of Children Treated for Acute Lymphoblastic Leukemia

The purpose of this study was to investigate whether the intelligence quotient (IQ) in children treated for leukemia decreases in the years following whole brain irradiation. Twenty-seven leukemic children were assessed following a mean time lapse between radiotherapy and IQ measurement of 9 years. The IQ test used was the Hamburg Weschsler Intelligence Test for Adults. The IQ results did not differ significantly, p > 0.05, from the IQs of the general population. It was found that age and dose were not predictors of a decrease in IQ. The only predictor was time lapse between irradiation and IQ measurement, which we found to be indicative of an IQ decrease even after 9 years. Time lapse between irradiation is a useful predictor of IQ.

Radiotherapy with Different Fractionations and Simultaneous Cisplatin or Carboplatin in the Treatment of Advanced Head and Neck Carcinomas: Clinical Results and Radiobiological Investigations

Head and neck cancers can be treated with curative intent in the early stages by surgery or radiotherapy. Locally advanced carcinomas may not be controlled by single modality therapy, and local progression is the predominant cause of death. Radio-chemotherapy is gaining importance as primary treatment (Al-Sarraf 1988). Mitomycin-C, 5-fluorouracil (5-FU), bleomycin, methotrexate, and platinum derivatives have been used simultaneously with radiotherapy and have proven to be effective (Bachaud et al. 1991; Fu et al. 1987; Marcial et al. 1988; Sanchiz et al. 1990; Schnabel et al. 1991, 1992; Weissenberg et al. 1989; Wendt et al. 1988; Zamboglou et al. 1992). Unfortunately, some of these agents enhance mucosal reactions of concomitant radiotherapy (Fu et al. 1987; Wendt et al. 1988). In contrast, platinum derivatives do not enhance mucositis (Zambouglou et al. 1989, 1992). We report here on our experience using conventional and hyperfractionated, accelerated radiotherapy in combination with cisplatin and carboplatin in the management of advanced head and neck carcinomas as well as radiobiological investigations.