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Should Sentinel Lymph Node (SLN) Biopsies Be Routinely Performed for Melanomas ≤1mm Thick? M
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS the 2 cancers were not seen on routine imaging. Routine imaging did not reveal any additional cancers during the study period. Overall, the rate of new cancer detection on surveillance MRI during the study period was 0.9% (2 of 202 imaging studies). Patient age, Gail score, tumor stage, grade, receptor status (estrogen, progesterone, and Her2neu), and surgical treatment were not predictive of MRI surveillance use. Conclusion: Prospective studies are needed to determine which patients would potentially benefit from breast MRI surveillance following curative-intent treatment. The lack of standardized guidelines may result in excessive or inappropriate use, unnecessary follow-up procedures, and a concomitant low yield.
26.9. Clinical Follow-Up Strategies after Potentially Curative Therapy of Ovarian Cancer. G. Harmandayan,1 K. S. Virgo,2 F. Gao,3 D. G. Mutch,3 F. E. Johnson2; 1Saint Louis University, Saint Louis, MO; 2Saint Louis University, Saint Louis, MO; 3 Washington University, Saint Louis, MO Background: Surveillance of patients after potentially curative resection of ovarian carcinoma has important clinical, legal, and financial implications for patients, physicians, and society. The specific modalities used in surveillance by clinicians, and how frequently they are recommended, are not known at present. The purpose of this study was to determine the current follow-up practice patterns of highly credentialed experts who treat patients with ovarian cancer and also provide care for them after initial treatment. Materials and Methods: We created a custom-designed survey featuring vignettes describing 4 patients with ovarian carcinoma of different stages and questions based on the vignettes. Surveys were mailed to the 943 members of the Society of Gynecologic Oncologists (SGO). The survey requested demographic information. Those indicating that they performed ovarian cancer surgery and also participated in long-term follow-up care were asked how often they requested 11 discrete follow-up evaluations (office visit, pelvic examination, Pap smear, complete blood count, comprehensive metabolic panel, serum CA-125 level, transvaginal ultrasound, chest X-ray, abdominal-pelvic CT, chest CT and abdominal-pelvic MRI) for their patients treated for cure in the first ten post-operative years. These 11 modalities include all that are mentioned in the relevant medical literature. Simple descriptive statistics (means, standard deviations, medians and ranges) were calculated. Results: Of the 943 gynecologic oncologists surveyed, 323 (34%) responded and 283 (30%) provided evaluable responses. The most frequently recommended modalities for each year were office visit, pelvic examination and serum CA-125 level. There was marked variability in the recommended frequency of surveillance modalities. For example, the number of office visits recommended in post-operative year 1 for patients with stage III ovarian carcinoma with > 1 cm3 of residual cancer after surgery ranged from 2-12. Imaging studies (chest X-ray, abdominal-pelvic CT, transvaginal ultrasound, etc.) were rarely recommended. The frequency of testing decreased with increasing post-operative years for all tests that were commonly used. For example, the median number of times the serum CA-125 level was recommended for high-risk stage III patients was 4 during the first year, tapering to 1 by years 5. Conclusion: To our knowledge, the value of routine follow-up testing in patients treated for ovarian cancer has not been well documented. There is little agreement in the literature about the most appropriate type and timing of surveillance methods needed. This is the first data on this topic, to our knowledge. Our data shows marked variability in the intensity of surveillance practice among SGO members. Further research should aim to identify the sources of this variability.
26.10. Should Sentinel Lymph Node (SLN) Biopsies Be Routinely Performed for Melanomas £1mm Thick? M. M. Peters, M. Hearn, J. C. Kairys, M. J. Mastrangelo, T. Sato, K. Feeney, A. C. Berger; Thomas Jefferson University, Philadelphia, PA
241
Introduction: Malignant melanoma is being increasingly diagnosed and is the sixth-leading cause of cancer deaths in the US. It is well-accepted that SLN is performed for melanomas between 1 and 4 mm. thick. However, there is still some controversy about SLN for thin (1 mm) melanomas which have a positivity rate of 3-6%. We reviewed our institutional experience to further explore this controversy. Methods: We reviewed our institutional database of patients treated at Thomas Jefferson University Hospital between 1980 and 2009 (n ¼ 1280) to find all patients who underwent SLN. The pathology reports were reviewed for important information about the primary such as thickness, Clark level, mitoses, regression, and ulceration; these were recorded in the database when available. There were a total of 639 patients who underwent SLN for whom information on Breslow thickness was available. Patients were grouped into T categories based on the 6th edition AJCC staging manual. Results: The average age of the SLN cohort was 56 years old. There were 375 males and 264 females. The overall SLN positivity rate was 15%. There were eight patients who underwent SLN with melanoma-in-situ because of concerns of extensive regression; all of these patients had a negative SLN biopsy. The average thickness for the other 631 patients was 2.3 mm and the median thickness was 1.4 mm (range-0.2 to 40 mm). SLN positivity by T stage is as follows: T1: 1.4%, T2: 11.3%, T3: 28.3%, and T4: 37.5%. The three patients with positive SLN in the T1 group had primary thicknesses of 0.6, 0.65, and 0.72. One of the three had documented mitoses in the primary pathology report. Conclusion: Positive SLN biopsies in patients with thin melanomas are very uncommon; in our series, this was 1.4%. This information should be used when counseling patients considering SLN for thin melanomas. 26.11. A Phase I Study of Bortezomib and Interferon-Alpha-2b in Patients with Metastatic Melanoma. V. P. Grignol, K. L. Kendra, G. B. Lesinski, T. Olenki, W. E. Carson, III; Ohio State University, Columbus, OH Background: We have previously shown that bortezomib and interferon-alpha (IFN) induce synergistic apoptosis in human melanoma cell lines and that cell death was dependent on caspase activation. The proapoptotic effects of this treatment combination were significantly reduced following inhibition of caspase-8 and in the presence of a dominant-negative form of the FADD protein or Fas-specific siRNA. Combined treatment with bortezomib and IFN also led to significant prolongation of survival in a murine model of melanoma and significantly reduced tumor growth in a xenograft model of human melanoma compared with either agent alone. These studies showed that bortezomib plus IFN may have utility for the treatment of melanoma. The primary objective of the study was to determine the safety, tolerability and dose-limiting toxicity of bortezomib when administered in combination with interferon-alpha-2b (IFN) to patients with metastatic melanoma. Methods: Eligibility for this study included a diagnosis of metastatic cutaneous melanoma, an ECOG performance status of 2 or less, and normal organ and bone marrow function. There was no limit to the number of prior systemic therapies allowed. Adjuvant IFN was allowed if completed greater than 6 months prior to enrollment. Patients with stable treated brain metastases were allowed. Patients with greater than grade 2 peripheral neuropathy were excluded. During week 0, IFN was administered as a single agent at a dose of 5 million units (MU) per square meter (m2) subcutaneously (sc) on days 1, 3, and 5. In weeks 1 - 4, patients received combination therapy followed by a 1 week treatment break in week 5. Bortezomib was administered intraveneously (iv) on day 1 of the weekly cycle along with IFN at 5 MU/m2 sc on days 1, 3, and 5. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m2) to cohorts of three patients. This 5 week cycle was repeated for a total of six months. Patients that exhibited a clinical response or stabilization of disease were permitted to receive additional cycles of therapy. Staging scans were obtained after cycles 1, 3, and 5. Results: 16 patients were treated (8 females, 8 males). Their median age was 58.5 years (34-82). All primary melanomas arose in highly sun exposed areas and the majority (11 of 16) were Clark’s level IV or V. The average
26.9. Clinical Follow-Up Strategies after Potentially Curative Therapy of Ovarian Cancer. G. Harmandayan,1 K. S. Virgo,2 F. Gao,3 D. G. Mutch,3 F. E. Johnson2; 1Saint Louis University, Saint Louis, MO; 2Saint Louis University, Saint Louis, MO; 3 Washington University, Saint Louis, MO Background: Surveillance of patients after potentially curative resection of ovarian carcinoma has important clinical, legal, and financial implications for patients, physicians, and society. The specific modalities used in surveillance by clinicians, and how frequently they are recommended, are not known at present. The purpose of this study was to determine the current follow-up practice patterns of highly credentialed experts who treat patients with ovarian cancer and also provide care for them after initial treatment. Materials and Methods: We created a custom-designed survey featuring vignettes describing 4 patients with ovarian carcinoma of different stages and questions based on the vignettes. Surveys were mailed to the 943 members of the Society of Gynecologic Oncologists (SGO). The survey requested demographic information. Those indicating that they performed ovarian cancer surgery and also participated in long-term follow-up care were asked how often they requested 11 discrete follow-up evaluations (office visit, pelvic examination, Pap smear, complete blood count, comprehensive metabolic panel, serum CA-125 level, transvaginal ultrasound, chest X-ray, abdominal-pelvic CT, chest CT and abdominal-pelvic MRI) for their patients treated for cure in the first ten post-operative years. These 11 modalities include all that are mentioned in the relevant medical literature. Simple descriptive statistics (means, standard deviations, medians and ranges) were calculated. Results: Of the 943 gynecologic oncologists surveyed, 323 (34%) responded and 283 (30%) provided evaluable responses. The most frequently recommended modalities for each year were office visit, pelvic examination and serum CA-125 level. There was marked variability in the recommended frequency of surveillance modalities. For example, the number of office visits recommended in post-operative year 1 for patients with stage III ovarian carcinoma with > 1 cm3 of residual cancer after surgery ranged from 2-12. Imaging studies (chest X-ray, abdominal-pelvic CT, transvaginal ultrasound, etc.) were rarely recommended. The frequency of testing decreased with increasing post-operative years for all tests that were commonly used. For example, the median number of times the serum CA-125 level was recommended for high-risk stage III patients was 4 during the first year, tapering to 1 by years 5. Conclusion: To our knowledge, the value of routine follow-up testing in patients treated for ovarian cancer has not been well documented. There is little agreement in the literature about the most appropriate type and timing of surveillance methods needed. This is the first data on this topic, to our knowledge. Our data shows marked variability in the intensity of surveillance practice among SGO members. Further research should aim to identify the sources of this variability.
26.10. Should Sentinel Lymph Node (SLN) Biopsies Be Routinely Performed for Melanomas £1mm Thick? M. M. Peters, M. Hearn, J. C. Kairys, M. J. Mastrangelo, T. Sato, K. Feeney, A. C. Berger; Thomas Jefferson University, Philadelphia, PA
241
Introduction: Malignant melanoma is being increasingly diagnosed and is the sixth-leading cause of cancer deaths in the US. It is well-accepted that SLN is performed for melanomas between 1 and 4 mm. thick. However, there is still some controversy about SLN for thin (1 mm) melanomas which have a positivity rate of 3-6%. We reviewed our institutional experience to further explore this controversy. Methods: We reviewed our institutional database of patients treated at Thomas Jefferson University Hospital between 1980 and 2009 (n ¼ 1280) to find all patients who underwent SLN. The pathology reports were reviewed for important information about the primary such as thickness, Clark level, mitoses, regression, and ulceration; these were recorded in the database when available. There were a total of 639 patients who underwent SLN for whom information on Breslow thickness was available. Patients were grouped into T categories based on the 6th edition AJCC staging manual. Results: The average age of the SLN cohort was 56 years old. There were 375 males and 264 females. The overall SLN positivity rate was 15%. There were eight patients who underwent SLN with melanoma-in-situ because of concerns of extensive regression; all of these patients had a negative SLN biopsy. The average thickness for the other 631 patients was 2.3 mm and the median thickness was 1.4 mm (range-0.2 to 40 mm). SLN positivity by T stage is as follows: T1: 1.4%, T2: 11.3%, T3: 28.3%, and T4: 37.5%. The three patients with positive SLN in the T1 group had primary thicknesses of 0.6, 0.65, and 0.72. One of the three had documented mitoses in the primary pathology report. Conclusion: Positive SLN biopsies in patients with thin melanomas are very uncommon; in our series, this was 1.4%. This information should be used when counseling patients considering SLN for thin melanomas. 26.11. A Phase I Study of Bortezomib and Interferon-Alpha-2b in Patients with Metastatic Melanoma. V. P. Grignol, K. L. Kendra, G. B. Lesinski, T. Olenki, W. E. Carson, III; Ohio State University, Columbus, OH Background: We have previously shown that bortezomib and interferon-alpha (IFN) induce synergistic apoptosis in human melanoma cell lines and that cell death was dependent on caspase activation. The proapoptotic effects of this treatment combination were significantly reduced following inhibition of caspase-8 and in the presence of a dominant-negative form of the FADD protein or Fas-specific siRNA. Combined treatment with bortezomib and IFN also led to significant prolongation of survival in a murine model of melanoma and significantly reduced tumor growth in a xenograft model of human melanoma compared with either agent alone. These studies showed that bortezomib plus IFN may have utility for the treatment of melanoma. The primary objective of the study was to determine the safety, tolerability and dose-limiting toxicity of bortezomib when administered in combination with interferon-alpha-2b (IFN) to patients with metastatic melanoma. Methods: Eligibility for this study included a diagnosis of metastatic cutaneous melanoma, an ECOG performance status of 2 or less, and normal organ and bone marrow function. There was no limit to the number of prior systemic therapies allowed. Adjuvant IFN was allowed if completed greater than 6 months prior to enrollment. Patients with stable treated brain metastases were allowed. Patients with greater than grade 2 peripheral neuropathy were excluded. During week 0, IFN was administered as a single agent at a dose of 5 million units (MU) per square meter (m2) subcutaneously (sc) on days 1, 3, and 5. In weeks 1 - 4, patients received combination therapy followed by a 1 week treatment break in week 5. Bortezomib was administered intraveneously (iv) on day 1 of the weekly cycle along with IFN at 5 MU/m2 sc on days 1, 3, and 5. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m2) to cohorts of three patients. This 5 week cycle was repeated for a total of six months. Patients that exhibited a clinical response or stabilization of disease were permitted to receive additional cycles of therapy. Staging scans were obtained after cycles 1, 3, and 5. Results: 16 patients were treated (8 females, 8 males). Their median age was 58.5 years (34-82). All primary melanomas arose in highly sun exposed areas and the majority (11 of 16) were Clark’s level IV or V. The average