3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

PURPOSE: Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. PATIENTS AND METHODS: Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) < or = 10 ng/ml, Gleason score < or = 7 and clinical stage < or = T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT((R)) was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D(ref)) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D(90), D(10) urethra, and D(10) rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales. RESULTS: Median D(90) was 106% of D(ref) (range: 93-115%), median D(10) urethra 159% of D(ref) (range: 127-192%), and median D(10) rectum 55% of D(ref) (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. CONCLUSION: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.     

Long-Term Results in Three-Dimensional Conformal Radiotherapy of Localized Prostate Cancer at Moderate Dose (66 Gy)

PURPOSE: Biochemical control (bNED), disease-specific survival (DSS), overall survival (OS), and late gastrointestinal (GI) and urogenital (UG) side effects (EORTC/RTOG) of patients with long-term follow-up were evaluated. PATIENTS AND METHODS: Three-dimensional radiotherapy up to 66 Gy with/without additional hormonal therapy was performed in 154 prostate cancer (T1-3 N0 M0) patients. According to T-stage, pretreatment prostate-specific antigen (PSA) and grading, patients were divided into a low-, intermediate-, and high-risk group. The 5-, 8-, and 10-year actuarial rates of bNED, DSS and OS and late side effects were calculated. RESULTS: Median follow-up was 80 months. Additional hormonal therapy was given in 57% of patients. Distribution concerning risk groups (low, intermediate, high) showed 15%, 49%, and 36% of patients, respectively. bNED 5-, 8-, and 10-year actuarial rates were 46%, 44%, and 44%. DSS 5-, 8- and 10-year rates amounted to 96%, 90%, and 82%. OS 5-, 8- and 10-year rates were 81%, 64%, and 56%. In uni- and multivariate analysis, only pretreatment PSA (<10 vs. >or=10 ng/ml; p<0.05) and PSA nadir (<0.5 vs. >or=0.5 ng/ml; p<0.0001) affected bNED significantly. Age, risk group, T-stage, grading, and hormonal therapy had no significant influence on bNED, DSS, and OS. Rates of late GI and UG side effects grade>or=2 at 5 years were 17% and 15%. CONCLUSION: Current dose escalation studies with better bNED rates may be able to further increase long-term clinical outcome.     

Localized Prostate Cancer in Elderly Patients Outcome after Radiation Therapy Compared to Matched Younger Patients

PURPOSE: To detect a difference in outcome (disease-specific survival, local tumor progression, late toxicity, quality of life) after curative radiotherapy for localized prostate cancer in elderly as compared to younger patients. PATIENTS AND METHODS: In a retrospective analysis 59 elderly patients (> 74 years old) were matched 1:2 with younger patients from the data base according to tumor stage, grading, pre-treatment PSA values and year of radiotherapy. Surviving patients were contacted to fill in a validated questionnaire for quality of life measurement (EORTC QLQ-C30). Median follow-up for elderly and younger patients was 5.2 and 4.5 years, respectively. RESULTS: Overall survival at 5 years was 66% for the elderly and 80% for younger patients. Intercurrent deaths were observed more frequently in the elderly population. There was no age-specific difference in disease-specific survival (78% vs 82%), late toxicity or quality of life. Clinically meaningful local tumor progression was observed in 15% and 14%, respectively, corresponding to data from the literature following hormonal ablation. CONCLUSIONS: There is no obvious difference in outcome including disease-specific survival, late toxicity and quality of life in elderly patients, compared to a matched younger population. A clinically meaningful local tumor progression following radiotherapy or hormonal ablation only is rare. Local radiotherapy or, alternatively, hormonal ablation is recommended to preserve local progression-free survival in elderly patients except for very early stage of disease (i.e. T1 G1-2 M0).     

Value and Perspectives of Proton Radiation Therapy for Limited Stage Prostate Cancer

Background: This review article will focus on clinical results and limitations of proton beam irradiation. Possible technological, biological and medical perspectives will be addressed. Patients and Methods: A total of 911 patients with limited stage prostate cancer were treated with proton beam irradiation at Loma Linda University between 1991 and 1996. Endpoints of this evaluation were biochemically no evidence of disease survival (bNED) as well as acute and late treatment-related toxicity. Results: The bNED survival rate was 82% at 5 years. Among 870 patients evaluable for late toxicity the following late effects were observed: Grade 3/4: 0%, Grade 2 rectal: 3.5% and bladder: 5.4%. Conclusions: Despite relatively short follow-up times it seems justified to conclude that proton beam irradiation of prostate cancer can improve bNED rates by 10% and decrease Grade 2 late effects by more than 10%. There were no Grade 3 and 4 late effects. Hintergrund: Es werden Möglichkeiten und Grenzen der Protonenbestrahlung kritisch beleuchtet. Zudem wird ein Ausblick auf mögliche technologische, biologische und medizinische Perspektiven im Zusammenhang mit der Protonentherapie aufgezeigt. Patienten und Methoden: Grundlage der Auswertung bilden 911 Patienten mit einem lokal begrenzten Prostatakarzinom, die von 1991 bis 1996 an der Universität von Loma Linda eine externe Radiotherapie mit Protonen erhielten. Die Endpunkte der Untersuchung waren das biochemische rezidivfreie Überleben (bNED) sowie die akute und chronische Toxizität der Bestrahlung (RTOG). Ergebnisse: Nach fünf Jahren betrug das bNED (Kaplan-Meier) 82%. Unter 870 für die Frage der Spättoxizität auswertbaren Patienten wurden folgende Nebeneffekte beobachtet: Grad 3/4: 0%, Grad 2 Rektum: 3,5% und Blase: 5,4%. Schlußfolgerungen: Trotz der relativ kurzen Nachbeobachtungszeiten scheint der Schluß zulässig, daß die Protonenbestrahlung das biochemische rezidivfreie Überleben um ca. 10% zu verbessern und Grad-2-Späteffekte um mehr als 10% zu senken vermag. Grad-3/4-Toxizitäten wurden überhaupt nicht beobachtet.     

Value and Perspectives of Proton Radiation Therapy for Limited Stage Prostate Cancer

BACKGROUND: This review article will focus on clinical results and limitations of proton beam irradiation. Possible technological, biological and medical perspectives will be addressed. PATIENTS AND METHODS: A total of 911 patients with limited stage prostate cancer were treated with proton beam irradiation at Loma Linda University between 1991 and 1996. Endpoints of this evaluation were biochemically no evidence of disease survival (bNED) as well as acute and late treatment-related toxicity. RESULTS: The bNED survival rate was 82% at 5 years. Among 870 patients evaluable for late toxicity the following late effects were observed: Grade 3/4: 0%, Grade 2 rectal: 3.5% and bladder: 5.4%. CONCLUSIONS: Despite relatively short follow-up times it seems justified to conclude that proton beam irradiation of prostate cancer can improve bNED rates by 10% and decrease Grade 2 late effects by more than 10%. There were no Grade 3 and 4 late effects.     

The Impact of Varying Volumes in Rectal Balloons on Rectal Dose Sparing in Conformal Radiation Therapy of Prostate Cancer

BACKGROUND AND PURPOSE: The use of a rectal balloon leads to a protection of the posterior rectal wall in irradiation of prostate cancer. The purpose of this analysis was to quantitatively assess the optimal volume in rectal balloons concerning rectal dose sparing in different clinical target volumes (CTVs) in prostate cancer irradiation. PATIENTS AND METHODS: 14 patients with localized prostate cancer undergoing external beam radiotherapy were investigated. The prostate, the entire and the proximal seminal vesicles were delineated as CTV. Treatment plans without a rectal balloon and with a rectal balloon inflated with 40 ml (six patients) or 60 ml air (eight patients) were generated for each CTV and compared concerning rectal dose volume histograms. RESULTS: The use of a rectal balloon filled with 40 ml air led to no significant advantage in radiation exposure of the rectal wall in all CTVs. The use of a rectal balloon filled with 60 ml air resulted in a significant decrease of the exposed rectal wall volume in all CTVs with a reduced estimated risk for chronic toxicity in case of inclusion of the proximal or entire seminal vesicles into the CTV. CONCLUSION: The use of a rectal balloon filled with 60 ml air led to a significantly decreased proportion of the irradiated rectal wall for all CTVs. This volume filled in rectal balloons is therefore recommended for use. In case of irradiation of the prostate without the seminal vesicles, the use of a rectal balloon should be considered carefully concerning the patients' imaginable discomfort using a rectal balloon and a questionable advantage concerning the estimated risk for chronic toxicity.     

Selection and Delineation of Lymph Node Target Volume for Lung Cancer Conformal Radiotherapy Proposal for Standardizing Terminology Based on Surgical Experience

PURPOSE: To select and delineate the target volumes for definitive or postoperative radiotherapy for lung cancer. METHODS AND MATERIALS: The lymphatics of the lung and the dissemination of tumor cells to the intra- and extrathoracic lymph nodes are described. The incidence of involvement of the different lymph node sites in the chest is analyzed. The involvement of the contralateral hilar and/or supraclavicular lymph nodes and the consequences for target volume selection for curative radiotherapy are discussed. CT-based nodal classification and distribution of lymph nodes in the chest in CT-axial slices are presented. The sentinel node concept (SNC) and the preliminary data available for lung cancer are described. RESULTS: A critical review of the current TNM classification for lung cancer and the implications for target volume selection is given. The individual target volume selection and delineation have to be based on clinical and pathological data from large surgical. studies and upon the individual pathological and diagnostic patient data. The selection and delineation of the clinical target volumes for definitive and for postoperative radiotherapy, dependent on the lymph node involvement, are presented. CONCLUSIONS: Criteria for the selection and delineation of the clinical target volumes for definitive and for postoperative conformal radiotherapy in axial CT slices under consideration of site, size and stage of the lung cancer are described. Recommendations for target volume selection for definitive or postoperative radiotherapy are presented.     

CT精确定位扫描在鼻咽癌光子刀治疗中的应用

目的:探讨CT精确定位扫描在鼻咽癌(NPC)光子刀治疗中的应用价值。方法:对130例鼻咽部肿瘤患者行CT精确定位扫描,再将扫描图像传输到光子刀工作站,制定光子刀精确治疗计划,然后进行光子刀治疗。结果:130例NPC患者CT精确定位扫描操作规范,癌肿显示清晰,定位准确,误差<1mm,且定位范围完整。光子刀治疗3个月后CT复查均见病灶消失;6个月后复查,Ⅰ组有10例(21.74%)出现颞颌关节纤维化,Ⅱ组24例(39.34%),Ⅲ组10例(43.48%);12个月后复查,Ⅰ组未见放射性脑病,Ⅱ组有1例(1.64%),Ⅲ组有2例(8.70%)。结论:采用CT精确定位扫描及光子刀工作站制定精密的治疗计划,使NPC的光子刀治疗更精确。治疗后中远期并发症明显减少,获得了理想的治疗效果。     

Selective Lymph Node Dissection Following Hyperfractionated Accelerated Radio-(Chemo-)Therapy for Advanced Head and Neck Cancer

Background: 2-year results of a German multicenter randomized trial showed that accelerated chemoradiation with MMC/5-FU to 70.6 Gy is more effective than accelerated radiation to 77.6 Gy alone at equivalent levels of acute and late radiation morbidity. Frequency, histopathology and impact on local tumor control of selective lymph node dissection were analyzed. Patients and Methods: Between February 1996 and October 2000 at Tübingen University 42 randomized patients plus 45 non-randomized patients with stage III/IV M0 head and neck cancer were treated according to this protocol. After completion of hyperfractionated accelerated (chemo-)radiation a selective lymph node dissection was performed, if the primary tumor was in complete remission and clinical plus computed tomography proved residual lymph node disease. 17 of 38 patients with residual node metastasis underwent uni- or bilateral selective node dissection, the remaining patients had residual primary tumors, clinical deterioration or refused neck dissection. Results: After a median follow-up 26 months, the Kaplan-Meier analysis showed a 2-year overall survival of 49%, disease-specific survival of 64% and loco-regional tumor control of 60%, respectively. 3-year loco-regional tumor control in randomized patients was 52% compared to 58% in non-randomized patients (log rank p = 0.23). 2-year loco-regional tumor control in stage cT4cN0 was 76% compared to 57% in cT2-4 cN1-3 tumors. Subgroup analysis of patients with involved nodes revealed a 2-year loco-regional tumor control of 74% after complete remission of primary tumor and neck disease, 53% after complete remission of primary tumor and partial remission of neck disease. In patients with selective lymph node dissection loco-regional tumor control was 62%. Histopathological examination showed viable tumor in eight of 17 patients. Conclusions: Selective lymph node dissection of residual neck masses after completion of hyperfractionated accelerated radio-(chemo-)therapy is likely to contribute to loco-regional tumor control in advanced head and neck cancer. Hintergrund: Die multizentrische Phase-III-Studie (ARO 95-6) zur akzelerierten hyperfraktionierten Strahlentherapie - 5-Fluorouracil/Mitomycin C bei lokal fortgeschrittenen Kopf-Hals-Tumoren konnte nachweisen, dass die kombinierte Radiochemotherapie bezüglich lokaler Tumorkontrolle und Gesamtüberleben wirksamer ist als die alleinige Strahlentherapie. Wir untersuchen Häufigkeit, histopathologisches Ergebnis und den Einfluss der selektiven Neck-Dissection auf die lokale Tumorkontrolle. Patienten und Methoden: Zwischen Februar 1996 und October 2000 wurden in Tübingen insgesamt 42 randomisierte und 45 nicht randomisierte Patienten mit fortgeschrittenen Kopf-Hals-Tumoren im Stadium III/IV M0 nach diesem Protokoll behandelt. Nach Abschluss der akzelerierten hyperfraktionierten Strahlentherapie - 5-Fluorouracil/Mitomycin C wurde eine selektive Neck-Dissection bei kompletter Remission des Primärtumors und partieller Remission der Halslymphknotenmetastasen angestrebt. Bei 17 von 38 Patienten mit residuellen Halslymphknotenmetastasen wurde eine uni- oder bilaterale selektive Neck-Dissection durchgeführt. Bei 21 Patienten wurde die Neck-Dissection wegen partieller Remission des Primärtumors, klinischer Verschlechterung oder Ablehnung durch den Patienten nicht durchgeführt. Ergebnisse: Nach einem medianen Follow-up von 26 Monaten betrugen das 2-Jahres-Gesamtüberleben 49%, das krankheitsspezifische Überleben 64% und die lokoregionäre Tumorkontrolle 60% (Kaplan-meier-Analyse). Für cT4-cN0-Tumoren betrug die lokoregionäre 2-Jahres-Tumorkontrolle 76% im Vergleich zu 57% bei cT2-cN1-3-Tumoren. Es bestand kein Unterschied bezüglich der lokoregionären Tumorkontrolle zwischen randomisierten und nicht randomisierten Patienten. Bei kompletter Remission des Primärtumors und der lokoregionären Lymphknoten betrug die 2-Jahres-Tumorkontrolle 74%, bei partieller Remission der lokoregionären Lymphknoten 53%. Nach partieller Remission der lokoregionären Lymphknoten und selektiver Neck-Dissection betrug die 2-Jahres-Tumorkontrolle 62% (Abbildung 3). Die histopathologische Aufarbeitung wies bei acht von 17 Patienten vitale Tumorzellen nach. Schlussfolgerungen: Die selektive Neck-Dissection von residuellen Halslymphknotenmetastasen nach akzelerierter hyperfraktionierter Strahlentherapie - 5-Fluorouracil/Mitomycin C bei lokal fortgeschrittenen Kopf-Hals-Tumoren kann möglicherweise zur lokalen Tumorkontrolle beitragen.     

Selective Lymph Node Dissection Following Hyperfractionated Accelerated Radio-(Chemo-)Therapy for Advanced Head and Neck Cancer

BACKGROUND: 2-year results of a German multicenter randomized trial showed that accelerated chemoradiation with MMC/5-FU to 70.6 Gy is more effective than accelerated radiation to 77.6 Gy alone at equivalent levels of acute and late radiation morbidity. Frequency, histopathology and impact on local tumor control of selective lymph node dissection were analyzed. PATIENTS AND METHODS: Between February 1996 and October 2000 at Tübingen University 42 randomized patients plus 45 non-randomized patients with stage III/IV MO head and neck cancer were treated according to this protocol. After completion of hyperfractionated accelerated (chemo-)radiation a selective lymph node dissection was performed, if the primary tumor was in complete remission and clinical plus computed tomography proved residual lymph node disease. 17 of 38 patients with residual node metastasis underwent uni- or bilateral selective node dissection, the remaining patients had residual primary tumors, clinical deterioration or refused neck dissection. RESULTS: After a median follow-up of 26 months, the Kaplan-Meier analysis showed a 2-year overall survival of 49%, disease-specific survival of 64% and loco-regional tumor control of 60%, respectively. 3-year loco-regional tumor control in randomized patients was 52% compared to 58% in non-randomized patients (log rank p = 0.23). 2-year loco-regional tumor control in stage cT4cN0 was 76% compared to 57% in cT2-4 cN1-3 tumors. Subgroup analysis of patients with involved nodes revealed a 2-year loco-regional tumor control of 74% after complete remission of primary tumor and neck disease, 53% after complete remission of primary tumor and partial remission of neck disease. In patients with selective lymph node dissection loco-regional tumor control was 62%. Histopathological examination showed viable tumor in eight of 17 patients. CONCLUSIONS: Selective lymph node dissection of residual neck masses after completion of hyperfractionated accelerated radio-(chemo-)therapy is likely to contribute to loco-regional tumor control in advanced head and neck cancer.     

Localized Prostate Cancer in Elderly Patients Outcome after Radiation Therapy Compared to Matched Younger Patients

Purpose: To detect a difference in outcome (disease-specific survival, local tumor progression, late toxicity, quality of life) after curative radiotherapy for localized prostate cancer in elderly as compared to younger patients. Patients and Methods: In a retrospective analysis 59 elderly patients (> 74 years old) were matched 1 : 2 with younger patients from the data base according to tumor stage, grading, pre-treatment PSA values and year of radiotherapy. Surviving patients were contacted to fill in a validated questionnaire for quality of life measurement (EORTC QLQ-C30). Median follow-up for elderly and younger patients was 5.2 and 4.5 years, respectively. Results: Overall survival at 5 years was 66% for the elderly and 80% for younger patients. Intercurrent deaths were observed more frequently in the elderly population. There was no age-specific difference in disease-specific survival (78% vs 82%), late toxicity or quality of life. Clinically meaningful local tumor progression was observed in 15% and 14%, respectively, corresponding to data from the literature following hormonal ablation. Conclusion: There is no obvious difference in outcome including disease-specific survival, late toxicity and quality of life in elderly patients, compared to a matched younger population. A clinically meaningful local tumor progression following radiotherapy or hormonal ablation only is rare. Local radiotherapy or, alternatively, hormonal ablation is recommended to preserve local progression-free survival in elderly patients except for very early stage of disease (i. e. T1 G1-2 M0). Ziel: Analyse des Krankheitsverlaufs (krankheitsspezifisches Überleben, lokale Tumorkontrolle, Spättoxizität, Lebensqualität) nach kurativer Radiotherapie eines nichtmetastasierten Prostatakarzinoms bei älteren Patienten im Vergleich zu jüngeren. Patienten und Methodik: Aus der Datenbank wurden den 59 über 74 Jahre alten Patienten im Verhältnis 1 : 2 jüngere Patienten zugeordnet, die im gleichen Zeitraum, mit gleichem Tumorstadium, histologischem Differenzierungsgrad, PSA sowie gleicher Vorbehandlung bestrahlt worden waren. Die noch lebenden Patienten wurden schriftlich gebeten, einen validierten Fragebogen zur Lebensqualität (EORTC QLQ-C30) auszufüllen. Die mediane Beobachtungszeit für die älteren und jüngeren Patienten betrug 5,2 bzw. 4,5 Jahre. Ergebnisse: Das Fünf-Jahres-Überleben für die älteren bzw. jüngeren Patienten betrug 66% und 80%. Interkurrente Todesfälle waren im Kollektiv der Älteren häufiger. Krankheitsspezifisches Überleben (78% bzw. 82% nach fünf Jahren), Spättoxizität und Lebensqualität waren in beiden Alterskategorien gleich. Die Rate klinisch bedeutsamer lokaler Tumorprogredienz (15% bzw. 14% innerhalb von fünf Jahren) entspricht Angaben aus der Literatur nach alleiniger hormonablativer Therapie. Schlußfolgerungen: Ein altersspezifischer Unterschied des Krankheitsverlaufs inklusive Spättoxizität und Lebensqualität nach Radiotherapie wurde nicht beobachtet. Eine klinisch relevante lokale Tumorprogredienz nach Bestrahlung wie auch nach hormonablativer Behandlung ist selten. Außer in sehr frühen Stadien (T1 G1-2 M0) ist der Einsatz einer dieser beiden Behandlungen bei älteren Patienten zur Erzielung einer lebenslangen lokalen Tumorfreiheit zu empfehlen.