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Organ preservation in the treatment of penile cancer: To cut or not to cut
S430
I. J. Radiation Oncology
2160
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
A Three-Dimensional CT Based Analysis of Inter-Fraction Bladder Motion During Radiotherapeutic Treatment of Bladder Cancer
K. Roof,1 A. Mazal,1 S. Sarkar,1 A. Zietman,1 G. Chen,1 W. Shipley1 Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA
1
Purpose/Objective: Appropriate field margins for bladder irradiation are controversial. Difficulty in agreeing on the appropriate expansion of the planning bladder volume for a CTV is due to the paucity of data regarding bladder motion and volumetric changes. In this study, these changes are examined utilizing data obtained from serial CT scans in patients with muscle invasive bladder cancer undergoing radiation therapy. We also evaluate the target expansion necessary to geometrically cover the bladder wall in serial CT scans. Materials/Methods: Ten patients, seven men and three women, were prospectively studied with up to four serial CT scans obtained at weekly intervals. Tattoos defining isocenter were placed at the time of conventional simulation prior to the initial CT scan. Subjects were requested to empty their bladders immediately prior to imaging. Isocenters were marked at the time of scan using metallic BBs. Patients were aligned to isocenter and scanned. Bladders were contoured. The geometrical data were analyzed with two approaches. In the first approach, the outer bladder wall volumes of the initial CT scan were measured and symmetrically expanded in three dimensions with a 1 cm and 2 cm expansion. AP and lateral beams eye view (BEV) projections were generated. This template was then applied to subsequent BEV bladder projections generated from serial CT scans. Geometric coverage was scored as adequate when the bladder fell completely within the applied expansion. When coverage was inadequate we measured the distance of bladder extension beyond the expansion. The initial coverage analysis was performed by aligning the isocenters of each serial CT scan. Templates were subsequently applied through aligning the bladder centroid on the serial scans. In the second analysis approach, the excursions of the bladder walls in the three primary orthogonal planes were measured. Animations of the serial CT scans were generated to qualitatively assess factors contributing to bladder motion and deformation. Results: 37 of the 39 CT scans obtained were utilized. There were significant intra- and inter- individual variations in bladder volumes observed. The mean bladder volume was 98 cc ⫾ 41 cc (Range:33–171 cc). Intra-individual volumes varied as much as 130 cc. 26 of 27 (96%) serial contoured bladders were covered with a 2 cm expansion on the initial bladder contour regardless of the method of alignment. 1 cm expansions geometrically covered the bladder in 12 of 27 (44%) scans (initial scans from which expansion was generated were not included in the analysis) when isocentric alignment was used. The maximum excursion of bladder wall outside of the expansion was 1.6 cm with a mean of 0.47 cm and a SD of 0.34 cm. When alignment was performed using the centroid of the 1 cm expansion and the centroid of the bladder, 25 of 27 studies were adequately covered with the 1 cm expansion. By sampling along the principle planes we observed the greatest mean divergence to be in the cranial axis, 1.6 cm (range 0.9 –2.5), with the least variation in the anterior inferior direction at 0.4 cm (0 –1.2 cm). The mean variation in the posterior direction was 1.2 ⫾ 0.3 cm. Mean variation in other directions were ⬃ 0.8 ⫾ 0.4cm in the lateral, anterior and inferior directions. Conclusions: There is significant inter-fraction variation in bladder shape, volume and position during a course of external beam radiation therapy. These variations are highly patient dependent. Primary factors contributing to bladder motion include: bladder and rectal filling, displacement by small bowel and the bony anatomy of the pelvis. Even with strict instructions regarding bladder voiding, significant variation in bladder volumes were observed. The greatest degree of bladder wall positional change occurred in the cranial direction with the least variation in the antero-inferior direction, limited by the pubic symphysis. Bladder based alignment appears to result in improved geometric coverage indicating a potential advantage for organ based image guided patient alignment.
2161
Organ Preservation in the Treatment of Penile Cancer: To Cut or Not to Cut 1
A. Zouhair, P. Jichlinski,2 D. Weber,3 D. Azria,1 W. Jeanneret Sozzi,1 L. Guillou,4 R. O. Mirimanoff,1 M. Ozsahin1 Radiation Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, 2Urology, CHUV, Lausanne, Switzerland, 3Radiation Oncology, University Hospital, Geneva, Switzerland, 4Pathology, CHUV, Lausanne, Switzerland 1
Purpose/Objective: To assess prognostic factors, outcome, feasibility of penis preservation in penile cancer. Materials/Methods: Sixty patients with penile carcinoma were treated between 1962 and 2003. Median age was 61 years (35– 85). Anatomic site was glans in 24, prepuce in 16, shaft in 13, coronary in 4, prepuce and glans in 2, and shaft and prepuce in 1. There were 22 T1, 32 T2, 5 T3, and 1 TX tumors. N-stage consisted of 42 patients with N0, 13 with N1, 3 with N2, and 2 with N3. Eighteen patients had grade 1, 17 grade 2, and 14 grade 3 tumors (not determined in 11). Forty-five percent (n ⫽ 27) underwent a curative surgery: partial penectomy (n ⫽ 23) with (n ⫽ 8) or without (n ⫽ 15) lymph node dissection, or total penectomy (n ⫽ 4) with (n ⫽ 3) or without (n ⫽ 1) lymph node dissection. All but 5 patients (operated) underwent definitive (n ⫽ 33) or postoperative (n ⫽ 22) radiotherapy (RT) to the penis and inguinal lymph nodes (n ⫽ 23), penis alone with (n ⫽ 4) or without (n ⫽ 11) brachytherapy, inguinal lymph nodes alone (n ⫽ 12), or brachytherapy alone (n ⫽ 1). The median and mean follow-up period was 62 months (range: 6 – 454). Results: Median time to locoregional relapse was 14 moths (range: 5–139). There were local relapse in 22, regional relapse in 9, and 10 distant metastases (local and regional relapse were observed together in 3 patients). Local failure was observed in 3 out of 27 (11%) patients treated with surgery with or without postoperative RT vs. in 19 out of 33 (56%) treated with definitive RT (p ⫽ 0.0001). Sixteen (73%) out of 22 local failures were successfully salvaged with surgery. Among the 33 patients treated with definitive RT, local control was obtained with organ preservation in 13 (39%). In the remaining 20, 15 out of 19 local failures were salvaged by partial (n ⫽ 8) or total penectomy (n ⫽ 7), and 4 out of 19 local failures could by salvaged conservatively resulting an ultimate penis preservation rate of 17 out of 33 (52%) patients treated with definitive RT. In all patients, 5- and 10-year overall and cancer-specific survival rates were 43% and 25%, and 61% and 55%, respectively. The 5and 10- year local and locoregional control rates were 63% and 48%, and 50% and 39%, respectively. In patients treated with definitive RT, 5- and 10-year probability of surviving with penis was 43% and 26%, respectively. There was no difference in terms of 10-year cancer-specific survival between the patients treated with definitive RT with salvage surgery and primary surgery with or without postoperative RT (56% vs. 53%; p ⫽ 0.16; see figure). In multivariate analyses, independent factors
Proceedings of the 46th Annual ASTRO Meeting
influencing the survival were the N-classification (p ⫽ 0.01) and the pathological grade (p ⫽ 0.03). Surgery was the only independent factor predicting the local control. Conclusions: In patients with squamous cell carcinoma of the penis, local control is definitively superior with surgery. However, there is no difference in terms of survival between patients treated with surgery and those treated with definitive RT with salvage surgery, with 52% organ preservation.
2162
Treatment of Carcinoma of the Female Urethra by Primary External Beam and Interstitial Radiotherapy 1
A. Reyna, Z. Wajsman,2 R. A. Zlotecki1 1
Radiation Oncology, University of Florida, Gainesville, FL, 2Surgery, University of Florida, Gainesville, FL
Purpose/Objective: To evaluate the University of Florida’s 35-year experience with this rare and aggressive disease by analyzing the impact of tumor and treatment variables on the incidence and patterns of local, regional, and distant recurrence as well as survival outcomes. Materials/Methods: The medical records of all women with carcinoma of the urethra treated at the University of Florida with radiation therapy were retrospectively reviewed. Thirty patients were identified as having been treated with curative intent between 1966 and 2001. Their ages ranged from 39 to 88 years (median, 68). Twenty-four patients were treated with radiotherapy alone; 5 with external beam radiotherapy alone, 18 with external beam radiotherapy followed by brachytherapy, and one with brachytherapy alone. Five women were treated with external beam radiotherapy preoperatively, followed by either an anterior exenteration (n ⫽ 4) or a cystourethrectomy (n ⫽ 1). One patient was treated with preoperative external beam radiotherapy and brachytherapy followed by an anterior exenteration. The median treatment course was 50 Gy for external beam radiation therapy and 25 Gy for brachytherapy. The median follow-up time was 2.8 years with the majority of patients followed until the time of death. Univariate and actuarial statistical methods were used to analyze variables of prognostic significance and survival probability. Multivariate analysis was not performed due to the small sample size. Results: The 5-year absolute and cause-specific survival rates were 35% and 43%, respectively. Almost all disease recurrence, both local and distant, occurred within the first 2 years of follow-up. All of the patients who suffered a recurrence died with disease The 5-year actuarial probabilities of freedom-from local recurrence and freedom-from distant metastasis were 74% and 79%, respectively. The 5-year actuarial probability of freedom- from regional failure within the pelvis was only 58%. Univariate analysis indicated that the absence of primary tumor extension to the bladder neck and complete tumor response to radiotherapy treatment were prognostic for local-regional control and thus survival. Patients with tumor extension to the bladder neck had a 5-year cause-specific survival rate of only 13%, compared to 59% in patients without bladder extension (p ⫽ 0.03). Patients with a complete response to radiotherapy had a 2-year survival rate of 78%, whereas only 17% of patients with incomplete treatment responses were alive at 2-years (p ⫽ 0.0001). Nodal stage was found significantly predictive for cause-specific survival (p ⫽ 0.034). The presence or absence of vaginal wall extension was not predictive for the probability of complete response to treatment, local-regional control or cause-specific survival. The incidence of complications was significant with six cases of Radiation Therapy Oncology Group Grade 3– 4 acute genitourinary complications and 2 patients dying of treatment related complications. Conclusions: Tumor extension to the bladder neck, nodal disease at presentation, and an incomplete response to radiotherapy treatment were significant predictors for poor outcome in this retrospective analysis. Although radiotherapy is an effective treatment for carcinoma of the female urethra which preserves both anatomy and function, surgical resection should be considered for cases with bladder neck extension and as salvage treatment in patients who do not have a complete response to primary radiotherapy treatment.
S431
I. J. Radiation Oncology
2160
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
A Three-Dimensional CT Based Analysis of Inter-Fraction Bladder Motion During Radiotherapeutic Treatment of Bladder Cancer
K. Roof,1 A. Mazal,1 S. Sarkar,1 A. Zietman,1 G. Chen,1 W. Shipley1 Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA
1
Purpose/Objective: Appropriate field margins for bladder irradiation are controversial. Difficulty in agreeing on the appropriate expansion of the planning bladder volume for a CTV is due to the paucity of data regarding bladder motion and volumetric changes. In this study, these changes are examined utilizing data obtained from serial CT scans in patients with muscle invasive bladder cancer undergoing radiation therapy. We also evaluate the target expansion necessary to geometrically cover the bladder wall in serial CT scans. Materials/Methods: Ten patients, seven men and three women, were prospectively studied with up to four serial CT scans obtained at weekly intervals. Tattoos defining isocenter were placed at the time of conventional simulation prior to the initial CT scan. Subjects were requested to empty their bladders immediately prior to imaging. Isocenters were marked at the time of scan using metallic BBs. Patients were aligned to isocenter and scanned. Bladders were contoured. The geometrical data were analyzed with two approaches. In the first approach, the outer bladder wall volumes of the initial CT scan were measured and symmetrically expanded in three dimensions with a 1 cm and 2 cm expansion. AP and lateral beams eye view (BEV) projections were generated. This template was then applied to subsequent BEV bladder projections generated from serial CT scans. Geometric coverage was scored as adequate when the bladder fell completely within the applied expansion. When coverage was inadequate we measured the distance of bladder extension beyond the expansion. The initial coverage analysis was performed by aligning the isocenters of each serial CT scan. Templates were subsequently applied through aligning the bladder centroid on the serial scans. In the second analysis approach, the excursions of the bladder walls in the three primary orthogonal planes were measured. Animations of the serial CT scans were generated to qualitatively assess factors contributing to bladder motion and deformation. Results: 37 of the 39 CT scans obtained were utilized. There were significant intra- and inter- individual variations in bladder volumes observed. The mean bladder volume was 98 cc ⫾ 41 cc (Range:33–171 cc). Intra-individual volumes varied as much as 130 cc. 26 of 27 (96%) serial contoured bladders were covered with a 2 cm expansion on the initial bladder contour regardless of the method of alignment. 1 cm expansions geometrically covered the bladder in 12 of 27 (44%) scans (initial scans from which expansion was generated were not included in the analysis) when isocentric alignment was used. The maximum excursion of bladder wall outside of the expansion was 1.6 cm with a mean of 0.47 cm and a SD of 0.34 cm. When alignment was performed using the centroid of the 1 cm expansion and the centroid of the bladder, 25 of 27 studies were adequately covered with the 1 cm expansion. By sampling along the principle planes we observed the greatest mean divergence to be in the cranial axis, 1.6 cm (range 0.9 –2.5), with the least variation in the anterior inferior direction at 0.4 cm (0 –1.2 cm). The mean variation in the posterior direction was 1.2 ⫾ 0.3 cm. Mean variation in other directions were ⬃ 0.8 ⫾ 0.4cm in the lateral, anterior and inferior directions. Conclusions: There is significant inter-fraction variation in bladder shape, volume and position during a course of external beam radiation therapy. These variations are highly patient dependent. Primary factors contributing to bladder motion include: bladder and rectal filling, displacement by small bowel and the bony anatomy of the pelvis. Even with strict instructions regarding bladder voiding, significant variation in bladder volumes were observed. The greatest degree of bladder wall positional change occurred in the cranial direction with the least variation in the antero-inferior direction, limited by the pubic symphysis. Bladder based alignment appears to result in improved geometric coverage indicating a potential advantage for organ based image guided patient alignment.
2161
Organ Preservation in the Treatment of Penile Cancer: To Cut or Not to Cut 1
A. Zouhair, P. Jichlinski,2 D. Weber,3 D. Azria,1 W. Jeanneret Sozzi,1 L. Guillou,4 R. O. Mirimanoff,1 M. Ozsahin1 Radiation Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, 2Urology, CHUV, Lausanne, Switzerland, 3Radiation Oncology, University Hospital, Geneva, Switzerland, 4Pathology, CHUV, Lausanne, Switzerland 1
Purpose/Objective: To assess prognostic factors, outcome, feasibility of penis preservation in penile cancer. Materials/Methods: Sixty patients with penile carcinoma were treated between 1962 and 2003. Median age was 61 years (35– 85). Anatomic site was glans in 24, prepuce in 16, shaft in 13, coronary in 4, prepuce and glans in 2, and shaft and prepuce in 1. There were 22 T1, 32 T2, 5 T3, and 1 TX tumors. N-stage consisted of 42 patients with N0, 13 with N1, 3 with N2, and 2 with N3. Eighteen patients had grade 1, 17 grade 2, and 14 grade 3 tumors (not determined in 11). Forty-five percent (n ⫽ 27) underwent a curative surgery: partial penectomy (n ⫽ 23) with (n ⫽ 8) or without (n ⫽ 15) lymph node dissection, or total penectomy (n ⫽ 4) with (n ⫽ 3) or without (n ⫽ 1) lymph node dissection. All but 5 patients (operated) underwent definitive (n ⫽ 33) or postoperative (n ⫽ 22) radiotherapy (RT) to the penis and inguinal lymph nodes (n ⫽ 23), penis alone with (n ⫽ 4) or without (n ⫽ 11) brachytherapy, inguinal lymph nodes alone (n ⫽ 12), or brachytherapy alone (n ⫽ 1). The median and mean follow-up period was 62 months (range: 6 – 454). Results: Median time to locoregional relapse was 14 moths (range: 5–139). There were local relapse in 22, regional relapse in 9, and 10 distant metastases (local and regional relapse were observed together in 3 patients). Local failure was observed in 3 out of 27 (11%) patients treated with surgery with or without postoperative RT vs. in 19 out of 33 (56%) treated with definitive RT (p ⫽ 0.0001). Sixteen (73%) out of 22 local failures were successfully salvaged with surgery. Among the 33 patients treated with definitive RT, local control was obtained with organ preservation in 13 (39%). In the remaining 20, 15 out of 19 local failures were salvaged by partial (n ⫽ 8) or total penectomy (n ⫽ 7), and 4 out of 19 local failures could by salvaged conservatively resulting an ultimate penis preservation rate of 17 out of 33 (52%) patients treated with definitive RT. In all patients, 5- and 10-year overall and cancer-specific survival rates were 43% and 25%, and 61% and 55%, respectively. The 5and 10- year local and locoregional control rates were 63% and 48%, and 50% and 39%, respectively. In patients treated with definitive RT, 5- and 10-year probability of surviving with penis was 43% and 26%, respectively. There was no difference in terms of 10-year cancer-specific survival between the patients treated with definitive RT with salvage surgery and primary surgery with or without postoperative RT (56% vs. 53%; p ⫽ 0.16; see figure). In multivariate analyses, independent factors
Proceedings of the 46th Annual ASTRO Meeting
influencing the survival were the N-classification (p ⫽ 0.01) and the pathological grade (p ⫽ 0.03). Surgery was the only independent factor predicting the local control. Conclusions: In patients with squamous cell carcinoma of the penis, local control is definitively superior with surgery. However, there is no difference in terms of survival between patients treated with surgery and those treated with definitive RT with salvage surgery, with 52% organ preservation.
2162
Treatment of Carcinoma of the Female Urethra by Primary External Beam and Interstitial Radiotherapy 1
A. Reyna, Z. Wajsman,2 R. A. Zlotecki1 1
Radiation Oncology, University of Florida, Gainesville, FL, 2Surgery, University of Florida, Gainesville, FL
Purpose/Objective: To evaluate the University of Florida’s 35-year experience with this rare and aggressive disease by analyzing the impact of tumor and treatment variables on the incidence and patterns of local, regional, and distant recurrence as well as survival outcomes. Materials/Methods: The medical records of all women with carcinoma of the urethra treated at the University of Florida with radiation therapy were retrospectively reviewed. Thirty patients were identified as having been treated with curative intent between 1966 and 2001. Their ages ranged from 39 to 88 years (median, 68). Twenty-four patients were treated with radiotherapy alone; 5 with external beam radiotherapy alone, 18 with external beam radiotherapy followed by brachytherapy, and one with brachytherapy alone. Five women were treated with external beam radiotherapy preoperatively, followed by either an anterior exenteration (n ⫽ 4) or a cystourethrectomy (n ⫽ 1). One patient was treated with preoperative external beam radiotherapy and brachytherapy followed by an anterior exenteration. The median treatment course was 50 Gy for external beam radiation therapy and 25 Gy for brachytherapy. The median follow-up time was 2.8 years with the majority of patients followed until the time of death. Univariate and actuarial statistical methods were used to analyze variables of prognostic significance and survival probability. Multivariate analysis was not performed due to the small sample size. Results: The 5-year absolute and cause-specific survival rates were 35% and 43%, respectively. Almost all disease recurrence, both local and distant, occurred within the first 2 years of follow-up. All of the patients who suffered a recurrence died with disease The 5-year actuarial probabilities of freedom-from local recurrence and freedom-from distant metastasis were 74% and 79%, respectively. The 5-year actuarial probability of freedom- from regional failure within the pelvis was only 58%. Univariate analysis indicated that the absence of primary tumor extension to the bladder neck and complete tumor response to radiotherapy treatment were prognostic for local-regional control and thus survival. Patients with tumor extension to the bladder neck had a 5-year cause-specific survival rate of only 13%, compared to 59% in patients without bladder extension (p ⫽ 0.03). Patients with a complete response to radiotherapy had a 2-year survival rate of 78%, whereas only 17% of patients with incomplete treatment responses were alive at 2-years (p ⫽ 0.0001). Nodal stage was found significantly predictive for cause-specific survival (p ⫽ 0.034). The presence or absence of vaginal wall extension was not predictive for the probability of complete response to treatment, local-regional control or cause-specific survival. The incidence of complications was significant with six cases of Radiation Therapy Oncology Group Grade 3– 4 acute genitourinary complications and 2 patients dying of treatment related complications. Conclusions: Tumor extension to the bladder neck, nodal disease at presentation, and an incomplete response to radiotherapy treatment were significant predictors for poor outcome in this retrospective analysis. Although radiotherapy is an effective treatment for carcinoma of the female urethra which preserves both anatomy and function, surgical resection should be considered for cases with bladder neck extension and as salvage treatment in patients who do not have a complete response to primary radiotherapy treatment.
S431