Gabriela Studer

Dysphagia in head and neck cancer patients following intensity modulated radiotherapy (IMRT)

BackgroundTo evaluate the objective and subjective long term swallowing function, and to relate dysphagia to the radiation dose delivered to the critical anatomical structures in head and neck cancer patients treated with intensity modulated radiation therapy (IMRT, +/- chemotherapy), using a midline protection contour (below hyoid, ~level of vertebra 2/3).Methods82 patients with stage III/IV squamous cell carcinoma of the larynx, oropharynx, or hypopharynx, who underwent successful definitive (n = 63, mean dose 68.9Gy) or postoperative (n = 19, mean dose 64.2Gy) simultaneous integrated boost (SIB) -IMRT either alone or in combination with chemotherapy (85%) with curative intent between January 2002 and November 2005, were evaluated retrospectively. 13/63 definitively irradiated patients (21%) presented with a total gross tumor volume (tGTV) >70cc (82-173cc; mean 106cc). In all patients, a laryngo-pharyngeal midline sparing contour outside of the PTV was drawn. Dysphagia was graded according subjective patient-reported and objective observer-assessed instruments. All patients were re-assessed 12 months later. Dose distribution to the swallowing structures was calculated.ResultsAt the re-assessment, 32-month mean post treatment follow-up (range 16-60), grade 3/4 objective toxicity was assessed in 10%. At the 32-month evaluation as well as at the last follow up assessment mean 50 months (16-85) post-treatment, persisting swallowing dysfunction grade 3 was subjectively and objectively observed in 1 patient (1%). The 5-year local control rate of the cohort was 75%; no medial marginal failures were observed.ConclusionsOur results show that sparing the swallowing structures by IMRT seems effective and relatively safe in terms of avoidance of persistent grade 3/4 late dysphagia and local disease control.

Osteoradionecrosis of the mandible: Minimized risk profile following intensity-modulated radiation therapy (IMRT)

Background and Purpose:Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between < 1% and ~ 6%. Intensity-modulated radiation therapy (IMRT) is expected to translate into a further important reduction of ON. The aim of this descriptive study was to assess absolute and relative bone volumes exposed to high IMRT doses, related to observed bone tolerance.Patients and Methods:Between December 2001 and November 2004, 73 of 123 patients treated with IMRT were identified as subgroup “at risk” for ON (> 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12–46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance.Results:Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed.Conclusion:Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implants.Hintergrund und Ziel:Die Osteoradionekrose (ON) des Unterkiefers ist eine schwerwiegende Komplikation kurativer normofraktionierter Radiotherapie von Oropharynx- und Mundhöhlenkarzinomen. Nach Dosen zwischen 60 und 72 Gy besteht gemäß den Angaben einer Übersicht aus dem Jahr 1989 eine ON-Inzidenz von 5–15%, während laut neueren Arbeiten über leicht akzelerierte oder hyperfraktionierte Behandlungsschemata mit Dosen von 69–81 Gy die ON-Inzidenz zwischen < 1% und ca. 6% beträgt. Intensitätsmodulierte Radiotherapie (IMRT) dürfte die ON-Rate weiter reduzieren. Ziel dieser deskriptiven Arbeit war, absolute und relative Knochenvolumina mit hoher Dosisexposition zu evaluieren und in Beziehung zur beobachteten Knochentoleranz der eigenen Patienten nach IMRT-Behandlung zu setzen.Patienten und Methodik:Zwischen Dezember 2001 und November 2004 wurden an der eigenen Klinik 123 Patienten mit Tumoren der Kopf-Hals-Region mit IMRT behandelt; hiervon waren 73 einer Untergruppe von Patienten mit Risiko für ON zuzurechnen (Karzinome des Oropharynx oder der Mundhöhle und Herddosen > 60 Gy). 21 Patienten wurden postoperativ, 52 primär kurativ bestrahlt; 56 erhielten eine simultane cisplatinbasierte Chemotherapie. Die mittlere Beobachtungszeit betrug 22 Monate (12–46 Monate). Die Mundhöhle inkl. Kieferknochen außerhalb des Planungszielvolumens wurde konturiert, und Dosis-Volumen-Bedingungen zur Organschonung wurden festgelegt. Retrospektiv wurde für jeden Patienten das gesamte Kieferknochenvolumen konturiert, und die Dosis-Volumen-Histogramme wurden im Hinblick auf die klinische Knochentoleranz ausgewertet.Ergebnisse:Durch IMRT in Dosen zwischen 60 und 75 Gy (Mittelwert 67 Gy) wurden im Mittel 7,8, 4,8, 0,9 und 0,3 cm3 einer Dosis von > 60, 65, 70 und 75 Gy ausgesetzt (Tabelle 1 und Abbildung 1). Diese Werte sind deutlich kleiner als nach konventioneller Bestrahlung. Der Unterschied wurde im Vergleich mit einer historischen Serie näherungsweise quantifiziert (Abbildung 3). Zusätzliche Risikofaktoren der eigenen Patienten wurden analysiert (Abbildung 2). Nur ein ON-Ereignis (Grad 3) im Bereich des lingualen Horizontalasts der Mandibula wurde beobachtet und erfolgreich mit einer lingualen Dekortikation behandelt.Schlussfolgerung:Mittels IMRT werden nur sehr kleine Knochenvolumina hohen Bestrahlungsdosen ausgesetzt. Durch diese Knochenschonung werden eine weitere Reduktion des ON-Risikos und eine höhere Erfolgsrate rekonstruktiver Zahnimplantate (Tabelle 2) erwartet.

Outcome and prognostic factors in orbital lymphoma: a Rare Cancer Network study on 90 consecutive patients treated with radiotherapy.

PURPOSE To assess the outcome and prognostic factors in patients with orbital lymphoma treated by radiotherapy (RT). METHODS AND MATERIALS Between 1980 and 1999, 90 consecutive patients with primary orbital lymphoma were treated in 13 member institutions of the Rare Cancer Network. A full staging workup was completed in 56 patients. Seventy-eight patients had low-, 6 intermediate-, and 6 high-grade lymphoma, and 75 had a single orbital localization. All patients underwent RT with a median dose of 34.2 Gy (range 4.0-50.4). Eleven patients received chemotherapy in addition to RT. RESULTS After RT, local control was achieved in 97% of the patients. Local progression occurred in 2% and local relapse 1%. The rate of systemic relapse was 20%, and 9% of the patients developed metachronous contralateral eye involvement. The 5-year disease-free survival, overall survival, and cause-specific survival rate was 65%, 78%, and 87%, respectively. In univariate analyses, the statistically significant favorable prognostic factors were younger age, low grade, normal erythrocyte sedimentation rate, absence of muscular infiltration, complete response to treatment, conjunctival localization, and normal lactate dehydrogenase value for overall survival, disease-free survival, and freedom from treatment failure. In multivariate analysis, the favorable factors were younger age and low grade for overall and disease-free survival; a favorable response, conjunctival localization, and complete staging were highly significant for disease-free survival and freedom from treatment failure. Neither the RT technique nor the total dose influenced the outcome. Cataract and xerophthalmia were the most prominent late toxicities. CONCLUSION Moderate- to low-dose RT alone is able to control primary orbital lymphoma with low morbidity. A full staging workup is warranted in these patients. Prognostic factors were identified that could be useful in the overall management of this uncommon site of primary lymphoma.

Osteoradionecrosis of the Mandible

Background and Purpose:Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between < 1% and ~ 6%. Intensity-modulated radiation therapy (IMRT) is expected to translate into a further important reduction of ON. The aim of this descriptive study was to assess absolute and relative bone volumes exposed to high IMRT doses, related to observed bone tolerance.Patients and Methods:Between December 2001 and November 2004, 73 of 123 patients treated with IMRT were identified as subgroup “at risk” for ON (> 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12–46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance.Results:Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed.Conclusion:Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implants.Hintergrund und Ziel:Die Osteoradionekrose (ON) des Unterkiefers ist eine schwerwiegende Komplikation kurativer normofraktionierter Radiotherapie von Oropharynx- und Mundhöhlenkarzinomen. Nach Dosen zwischen 60 und 72 Gy besteht gemäß den Angaben einer Übersicht aus dem Jahr 1989 eine ON-Inzidenz von 5–15%, während laut neueren Arbeiten über leicht akzelerierte oder hyperfraktionierte Behandlungsschemata mit Dosen von 69–81 Gy die ON-Inzidenz zwischen < 1% und ca. 6% beträgt. Intensitätsmodulierte Radiotherapie (IMRT) dürfte die ON-Rate weiter reduzieren. Ziel dieser deskriptiven Arbeit war, absolute und relative Knochenvolumina mit hoher Dosisexposition zu evaluieren und in Beziehung zur beobachteten Knochentoleranz der eigenen Patienten nach IMRT-Behandlung zu setzen.Patienten und Methodik:Zwischen Dezember 2001 und November 2004 wurden an der eigenen Klinik 123 Patienten mit Tumoren der Kopf-Hals-Region mit IMRT behandelt; hiervon waren 73 einer Untergruppe von Patienten mit Risiko für ON zuzurechnen (Karzinome des Oropharynx oder der Mundhöhle und Herddosen > 60 Gy). 21 Patienten wurden postoperativ, 52 primär kurativ bestrahlt; 56 erhielten eine simultane cisplatinbasierte Chemotherapie. Die mittlere Beobachtungszeit betrug 22 Monate (12–46 Monate). Die Mundhöhle inkl. Kieferknochen außerhalb des Planungszielvolumens wurde konturiert, und Dosis-Volumen-Bedingungen zur Organschonung wurden festgelegt. Retrospektiv wurde für jeden Patienten das gesamte Kieferknochenvolumen konturiert, und die Dosis-Volumen-Histogramme wurden im Hinblick auf die klinische Knochentoleranz ausgewertet.Ergebnisse:Durch IMRT in Dosen zwischen 60 und 75 Gy (Mittelwert 67 Gy) wurden im Mittel 7,8, 4,8, 0,9 und 0,3 cm3 einer Dosis von > 60, 65, 70 und 75 Gy ausgesetzt (Tabelle 1 und Abbildung 1). Diese Werte sind deutlich kleiner als nach konventioneller Bestrahlung. Der Unterschied wurde im Vergleich mit einer historischen Serie näherungsweise quantifiziert (Abbildung 3). Zusätzliche Risikofaktoren der eigenen Patienten wurden analysiert (Abbildung 2). Nur ein ON-Ereignis (Grad 3) im Bereich des lingualen Horizontalasts der Mandibula wurde beobachtet und erfolgreich mit einer lingualen Dekortikation behandelt.Schlussfolgerung:Mittels IMRT werden nur sehr kleine Knochenvolumina hohen Bestrahlungsdosen ausgesetzt. Durch diese Knochenschonung werden eine weitere Reduktion des ON-Risikos und eine höhere Erfolgsrate rekonstruktiver Zahnimplantate (Tabelle 2) erwartet.

Osteoradionecrosis of the Mandibula in Patients Treated with Different Fractionations

Purpose:The incidence of osteonecrosis of the mandibula (ON) after irradiation using modern three-dimensional planning as well as hyperfractionation or moderately accelerated irradiation has been evaluated and compared with the incidence of the preceding period.Patients and Methods:The records of 268 head and neck cancer patients irradiated between January 1, 1980 and December 31, 1998 with a dose to the mandibula of at least 60 Gy were retrospectively analyzed. All patients had CT-based treatment planning, computerized dose calculation with isodose charts also in several off-axis planes, and regular verification films.Results:The long-term cumulative incidence of ON needing mandibular resection was as follows: after conventional fractionation 6.2% (between 60 and 66.6 Gy target dose) or 20.1% (between > 66.6 and 72 Gy); after hyperfractionated irradiation with a target dose between 72 and 78.8 Gy 6.6%; after concomitant boost irradiation according to the MDA/Houston regime with a dose between 63.9 and 70.5 Gy: no case; after 6 × 2 Gy/week or 7 × 1.8 Gy/week and a total target dose between 66 and 72 Gy approximately 17% or higher (small patient number).Conclusion:Comparison of the incidence of ON during the period between 1980 and 1990 with the following period between 1990 and 1998 shows a decrease in risk to a value of approximately 5% using modern three-dimensional techniques as well as hyperfractionation or moderately accelerated fractionation.Ziel:Die Inzidenz von Osteonekrosen (ON) der Mandibula nach Radiotherapie im Bereich von Mundhöhle und Pharynx nach Anwendung moderner dreidimensionaler Bestrahlungsplanung und veränderten Fraktionierungen wurde ermittelt und mit den Erfahrungen der unmittelbar vorausgegangenen Periode verglichen.Patienten und Methodik:Es handelt sich um eine retrospektive Analyse der Inzidenz von Mandibulanekrosen bei 268 Patienten mit Karzinomen der Mundhöhle oder des Pharynx, die zwischen dem 01.01.1980 und dem 31.12.1998 im Rahmen einer primären oder postoperativen Radiotherapie eine Dosis von mindestens 60 Gy auf die Mandibula erhalten hatten (Tabelle 1). Alle Patienten erhielten eine CT-unterstützte computerisierte Bestrahlungsplanung mit Isodosenkarten auch in mehreren Ebenen außerhalb des Zentralstrahls und regelmäßigen Feldkontrollaufnahmen.Ergebnisse:Die kumulative Inzidenz einer mit Mandibularesektion behandelten ON nach Bestrahlung betrug nach konventioneller Fraktionierung (Abbildung 1a) 6,2% (60–66,6 Gy) bzw. 20,1% (> 66,6–72 Gy), nach hyperfraktionierter Bestrahlung (Abbildung 1c) mit 72–78,8 Gy 6,6%; nach akzelerierter Bestrahlung (Abbildung 1b) gemäß dem Schema des MDA-Hospitals in Houston, TX, USA, mit einer Dosis von 63,9–70,5 Gy wurde keine ON beobachtet, während nach 6 × 2 Gy/Woche bzw. 7 × 1,8 Gy pro Woche und einer Gesamtdosis zwischen 66 und 72 Gy etwa 17% ON beobachtet wurden.Schlussfolgerung:Ein Vergleich der Inzidenz von ON der Mandibula nach Anwendung moderner dreidimensionaler Bestrahlungsplanung und hyperfraktionierter oder mäßig akzelerierter Bestrahlung mit gleichzeitigem Boost nach dem Schema des MDA-Hospitals zeigt gegenüber der Inzidenz in der vorausgegangenen Periode zwischen 1980 und etwa 1987 einen Rückgang auf Werte von etwa 5% (Tabelle 2).

IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients

BackgroundPreliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules.ResultsBetween 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given.SIB radiation schedules with 5–6 × 2 Gy/week to 60–70 Gy, 5 × 2.2 Gy/week to 66–68.2 Gy (according to the RTOG protocol H-0022), or 5 × 2.11 Gy/week to 69.6 Gy were used.After mean 18 months (10–44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients.Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session.ConclusionSIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Locoregional Failure Analysis in Head-and-Neck Cancer Patients Treated with IMRT

Purpose:Purpose: Analysis of locoregional failure in head-and-neck cancer (HNC) following intensity-modulated radiation therapy (IMRT), with focus on the location of locoregional failures in relation to the chosen planning target volumes (PTVs) and dose distributions.Patients and Methods:Between January 2002 and May 2006, 280 HNC patients were subjected to IMRT at the authors’ institution. Mean follow-up was 23.2 months (3–59.3 months). Definitive IMRT was performed in 75% of all patients. In 71%, simultaneous cisplatin-based chemotherapy was given. 70% of patients presented with T3/4, T1–2 N2c/3 or recurred disease. Locoregional failure patterns were analyzed.Results:2-year local, nodal, distant, disease-free, and overall survival rates were 80%, 87%, 87%, 73%, and 82%, respectively. 46 local (16%) and 31 nodal (11%) failures have been observed so far. Local tumor persistence was seen in 23/46 cases (50%), and nodal persistence in 12/31 (39%), respectively. One marginal local failure developed in a patient referred for a recurred oral cavity tumor. Three nodal failures developed outside the PTVs at unexpected locations. All other failures have been confirmed “in field”. No failure occurred in level Ib or upper level II. Local failure occurred mainly following definitive IMRT for large tumors, nodal failure only in nodally positive patients with nodal high-risk features.Conclusion:The dose-volume concept as used here has shown to be adequate, with disease failure developing at the site of the initial gross tumor manifestation inside the boost volume.Ziel:Analyse des lokoregionalen Tumorversagens nach intensitätsmodulierter Radiotherapie (IMRT), mit Fokus auf den Ort des Versagens in Bezug auf die konturierten Volumina bzw. die Dosisverteilung.Patienten und Methodik:Zwischen Januar 2002 und Mai 2006 wurden an der eigenen radioonkologischen Klinik 280 Patienten mit Kopf-Hals-Tumoren einer IMRT unterzogen. Die mittlere Beobachtungszeit beläuft sich auf 23,2 Monate (3–59,3 Monate). Bei 75% der Patienten wurde eine definitive IMRT durchgeführt. 71% der Patienten erhielten eine simultane Chemotherapie mit Cisplatin. 70% wurden mit fortgeschrittenen Stadien T3/4, T1–2 N2c/3 oder einem Rezidiv zugewiesen (Tabelle 2). Das lokoregionale Ereignismuster wurde analysiert.Ergebnisse:Die Lokal-, Nodal- und Fernkontrollraten nach 2 Jahren beliefen sich auf 80%, 87% und 87%, die krankheitsfreie bzw. Gesamtüberlebensrate betrug 73% und 82% (Tabelle 4). 46 Fälle (16%) lokalen und 31 (11%) nodalen Versagens wurden bislang festgestellt, die in 23/46 Fällen (50%) einer lokalen und in 12/31 Fällen (39%) einer nodalen Tumorpersistenz entsprachen. Nur ein Patient mit einem bereits rezidivierten Mundhöhlentumor entwickelte ein Feldrandrezidiv (Tabelle 1). Dreimal fand sich ein nodales Versagen außerhalb der Planungszielvolumina an unerwarteten Lokalisationen. Alle anderen Fälle von Versagen konnten als „im Feld“ befindlich bestätigt werden. Kein Versagen wurde im Lymphknotenlevel I oder kranial im Level II gefunden (Tabellen 5 und 6). Lokales Versagen erfolgte hauptsächlich bei primär bestrahlten Patienten mit großem Tumorvolumen (Abbildungen 1 und 2a); nodales Versagen fand sich ausschließlich bei initial nodal positiven Patienten mit nodalen Risikofaktoren (Tabelle 3, Abbildung 2b).Schlussfolgerung:Das hier verwendete Dosis-Volumen-Konzept erwies sich als adäquat, da der Großteil der Rückfälle am Ort der initialen Tumormanifestation, innerhalb des Boostvolumens, auftrat.

Volumetric staging (VS) is superior to TNM and AJCC staging in predicting outcome of head and neck cancer treated with IMRT

The UICC classification (TNM) represents the validated standard tool to describe tumor extent and includes prognostic information on the probability of disease control. The American Joint Committee on Cancer (AJCC) stage grouping is based on the evaluation of treatment and outcome. Gross tumor volume (GTV) might be more relevant than pure description (TNM) or stage grouping as prognostic factor for local control in head and neck cancer (HNC). Based on the observation of GTV-correlated outcome in our initial HNC patient cohort treated with IMRT, we tested the hypothesis that the GTV is the most reliable predictive tool in HNC outcome. A GTV based volumetric staging system (VS) was introduced, using two volumetric cut-off values (15 and 70 cm3). VS, TNM, and AJCC stages were assessed and correlated with outcome following primary radiation in 172 HNC patients. Analyses were based on Kaplan-Meier survival curves. VS proved to be superior to the TNM/AJCC in predicting outcome. In addition, VS enabled to stratify high- and low-risk patients in advanced TN stages. GTV represented the most important prognostic indicator in HNC treated with IMRT and is recommended to be considered for therapeutic decisions and estimation of outcome.

Outcome and patterns of failure in testicular lymphoma: a multicenter rare cancer network study

PURPOSE To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). METHODS AND MATERIALS Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). RESULTS After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. CONCLUSIONS In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.

PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison

BackgroundImpact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma.Patients and methodsForty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6–49 months) for the PET/CT-IMRT group and twenty eight months (range, 1–168 months) for the controls.ResultsPET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005).ConclusionPET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings.