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non-metastatic melanoma patients at high risk of recurrence?

Forums General Melanoma Community non-metastatic melanoma patients at high risk of recurrence?

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      JC
      Participant

      Can we ask for this test currently?  Should we?  Is this more predictive than Breslow?

      JC
      Participant

      Can we ask for this test currently?  Should we?  Is this more predictive than Breslow?

      JC
      Participant

      Can we ask for this test currently?  Should we?  Is this more predictive than Breslow?

      POW
      Participant

      Jerry, the article you linked to is a press release. As with most press releases, it puts a "spin" on the information that is designed to attract publilcity and investors. 

      When you read the original scientific articles by Dr. Gerami (see for example: http://www.archivesofpathology.org/doi/abs/10.1043/2011-0048-RAIR.1 ) what you learn is that this test (called a "FISH" test) is only designed to distinguish melanoma from nevi (ordinary moles) in the rare cases in which standard pathology results are ambiguous. That is a good thing, of course.

      But this test CAN NOT TELL patients with known Stage I or Stage II melanoma whether or not they are likely to progress. That "spin" is public relations bs.

      POW
      Participant

      Jerry, the article you linked to is a press release. As with most press releases, it puts a "spin" on the information that is designed to attract publilcity and investors. 

      When you read the original scientific articles by Dr. Gerami (see for example: http://www.archivesofpathology.org/doi/abs/10.1043/2011-0048-RAIR.1 ) what you learn is that this test (called a "FISH" test) is only designed to distinguish melanoma from nevi (ordinary moles) in the rare cases in which standard pathology results are ambiguous. That is a good thing, of course.

      But this test CAN NOT TELL patients with known Stage I or Stage II melanoma whether or not they are likely to progress. That "spin" is public relations bs.

      POW
      Participant

      Jerry, the article you linked to is a press release. As with most press releases, it puts a "spin" on the information that is designed to attract publilcity and investors. 

      When you read the original scientific articles by Dr. Gerami (see for example: http://www.archivesofpathology.org/doi/abs/10.1043/2011-0048-RAIR.1 ) what you learn is that this test (called a "FISH" test) is only designed to distinguish melanoma from nevi (ordinary moles) in the rare cases in which standard pathology results are ambiguous. That is a good thing, of course.

      But this test CAN NOT TELL patients with known Stage I or Stage II melanoma whether or not they are likely to progress. That "spin" is public relations bs.

      JC
      Participant

      I wonder if the genes being “turned on” are also linked to other characteristics, such as high mitotic rate or ulceration.  So, either way, there is the implication of higher risk.  I also wonder how this is reconciled with the Queensland Australia study showing 96% 20-year survival rate for Stage I thin lesions; did they look at this data on those lesions?  I also wonder what type of more aggressive treatment they’d offer Stage I/II patients anyway, it doesn’t seem like they’d start offering any adjuvant therapy to a Stage I patient

      JC
      Participant

      I wonder if the genes being “turned on” are also linked to other characteristics, such as high mitotic rate or ulceration.  So, either way, there is the implication of higher risk.  I also wonder how this is reconciled with the Queensland Australia study showing 96% 20-year survival rate for Stage I thin lesions; did they look at this data on those lesions?  I also wonder what type of more aggressive treatment they’d offer Stage I/II patients anyway, it doesn’t seem like they’d start offering any adjuvant therapy to a Stage I patient

      JC
      Participant

      I wonder if the genes being “turned on” are also linked to other characteristics, such as high mitotic rate or ulceration.  So, either way, there is the implication of higher risk.  I also wonder how this is reconciled with the Queensland Australia study showing 96% 20-year survival rate for Stage I thin lesions; did they look at this data on those lesions?  I also wonder what type of more aggressive treatment they’d offer Stage I/II patients anyway, it doesn’t seem like they’d start offering any adjuvant therapy to a Stage I patient

      Janner
      Participant

      I think this test is most often used to distinguish Spitz nevi from melanoma.  Spitz nevi are entirely benign and most often found on young individuals.  It looks almost identical to melanoma under the microscope.  So if a pathologist can't make the determination  of Spitz vs melanoma, the FISH test analyzes markers.  Lots of irregular gene findings means melanoma.  Normal gene findings means Spitz nevi.  I could be wrong, but I think this is most likely the major application of this test.

      JC
      Participant

      if it's just distinguishing spitz nevi from melanoma, then what's the "Kaplan-Meier analysis for 5-year metastasis free survival rates were 98% for Class 1 (low risk) and 37% for Class 2 (high risk)" referring to? 

      Janner
      Participant

      If you read the actual paper and not the press release, it says they are determining a diagnosis between melanoma/spitz or atypical/melanoma and more.

      In all cases, preliminary diagnoses were rendered before sending a tissue for FISH analysis. In most cases, the histologic differential diagnosis was between Spitz nevus and spitzoid melanoma or between atypical nevus (such as variants of deep penetrating/clonal/inverted type-A nevus, pigmented spindle cell nevus, atypical genital nevus, atypical conjunctival nevus showing cytologic atypia, mitotic activity, limited maturation, or proliferative nodules, among others) and nevoid melanoma (Table 1). In some cases, diagnostic considerations included dysplastic nevus and superficial spreading melanoma. In 2 cases, FISH was performed to confirm a suspected but histologically challenging diagnosis of nonsarcomatoid desmoplastic melanoma. At the time of preliminary diagnosis, based on histologic features, each lesion was designated as likely representing an atypical nevus (favoring a benign type), a truly borderline lesion, or a melanoma. These designations reflect the most likely interpretation if FISH was not performed.

      I picked this little sentence out later, which basically sums most of it up for me:

      Obviously, a FISH test is not needed for histologically unequivocal cases. The only current justification for use of this expensive test in a diagnostic setting is to employ it as a diagnostic adjunct to help classify histologically ambiguous lesions.

      I don't have time at the moment to go back and read the hype, but I think the actual study does a good job of describing the purpose and usage for this test.

      http://www.archivesofpathology.org/doi/full/10.5858/arpa.2011-0673-OA

      POW
      Participant

      If you look at the original scientific papers, you will see that the authors did a "retrospective" study. They collected OLD biopsy specimens in parafin (for microscopic analysis) and did their test. When they did the FISH test on "ambiguous" specimens (i.e., the original pathology could not say for sure), if the FISH test was strongly positive and then they looked at the patients' historical records, those patients turned out to have no evidence of melanoma in later years. When the FISH test on the ambiguous specimens was negative, those patients turned out not to have melanoma in later years. Therefore, the authors decided to designate FISH negative as "low risk" and FISH positive as "high risk". Confusing, I know.

      POW
      Participant

      Oops! I mis-typed. Positive FISH = later melanoma; negative FISH=no later melanoma on AMBIGUOUS specimens only.

      But Janner said it better (above) so ignore everything I said, anyway.

      JerryfromFauq
      Participant

      I don't see anything about this being an approved test yet.  While it apperently has a relationship with the FISH test, it seems to be a newer effort to help narrow down the cases that are the most likely (statistically) to re-occur.  

      http://skinmelanoma.com/health-care-professionals/prospective-clinical-validation/

      http://skinmelanoma.com/health-care-professionals/potential-clinical-benefits/

      Potential Clinical Benefits

      Knowing which Stage I and II patients are at high risk should significantly impact management of their disease

      The AJCC prognostic criteria are the traditional standard for staging cutaneous melanoma (Balch, CM, et. al., Melanoma of the Skin, 2009). However, histopathologic techniques alone do not optimally identify patients at high risk for metastasis. For instance, while Stage I melanomas are considered low risk as a group, some patients do metastasize and are at high risk for metastasis (Balch, 2009).

      There is also poor accuracy for predicting those Stage II patients at high risk for metastasis. Under the current staging system, the 5-year survival rate for clinical Stage II subjects is 53-82%, which overlaps significantly with the survival rate of 22-68% for Stage III cases (Balch, CM, et. al., 2009, 2010). In fact, Stage IIB and IIC patients have a worse 5-year survival rate than stage IIIA patients. These data indicate that there are a significant number of Stage II patients that are not accurately diagnosed as high risk using the current prognostic tools.

      Sentinel lymph node status has been reported as the most accurate prognostic factor for metastatic activity and survival (Gershenwald, JE, et. al., 1999; Morton, DL, et. al., 2006). However, of the 60,000 patients diagnosed with Stage I or II disease last year, up to 8,500 will develop distant metastatic disease within five years of diagnosis (Kalady, MF, et. al., 2003).

      The potential impact on clinical management for Stage I or II melanoma is significant given that the 5-year metastasis risk for DecisionDx-Melanoma Class 2 melanoma is greater than that of AJCC Stage III melanoma. For example, Class 2 patients may benefit from referral to a surgeon or oncologist for consideration of higher intensity monitoring, repeat lymph node mapping, lymph node dissection, adjuvant treatment and clinical trials.

      Also, while it is not often the urgent focus of oncology management discussions, the impact of the relatively good news of receiving a Class 1, low-risk designation should not be underestimated.

      JerryfromFauq
      Participant

      I don't see anything about this being an approved test yet.  While it apperently has a relationship with the FISH test, it seems to be a newer effort to help narrow down the cases that are the most likely (statistically) to re-occur.  

      http://skinmelanoma.com/health-care-professionals/prospective-clinical-validation/

      http://skinmelanoma.com/health-care-professionals/potential-clinical-benefits/

      Potential Clinical Benefits

      Knowing which Stage I and II patients are at high risk should significantly impact management of their disease

      The AJCC prognostic criteria are the traditional standard for staging cutaneous melanoma (Balch, CM, et. al., Melanoma of the Skin, 2009). However, histopathologic techniques alone do not optimally identify patients at high risk for metastasis. For instance, while Stage I melanomas are considered low risk as a group, some patients do metastasize and are at high risk for metastasis (Balch, 2009).

      There is also poor accuracy for predicting those Stage II patients at high risk for metastasis. Under the current staging system, the 5-year survival rate for clinical Stage II subjects is 53-82%, which overlaps significantly with the survival rate of 22-68% for Stage III cases (Balch, CM, et. al., 2009, 2010). In fact, Stage IIB and IIC patients have a worse 5-year survival rate than stage IIIA patients. These data indicate that there are a significant number of Stage II patients that are not accurately diagnosed as high risk using the current prognostic tools.

      Sentinel lymph node status has been reported as the most accurate prognostic factor for metastatic activity and survival (Gershenwald, JE, et. al., 1999; Morton, DL, et. al., 2006). However, of the 60,000 patients diagnosed with Stage I or II disease last year, up to 8,500 will develop distant metastatic disease within five years of diagnosis (Kalady, MF, et. al., 2003).

      The potential impact on clinical management for Stage I or II melanoma is significant given that the 5-year metastasis risk for DecisionDx-Melanoma Class 2 melanoma is greater than that of AJCC Stage III melanoma. For example, Class 2 patients may benefit from referral to a surgeon or oncologist for consideration of higher intensity monitoring, repeat lymph node mapping, lymph node dissection, adjuvant treatment and clinical trials.

      Also, while it is not often the urgent focus of oncology management discussions, the impact of the relatively good news of receiving a Class 1, low-risk designation should not be underestimated.

      JerryfromFauq
      Participant

      I don't see anything about this being an approved test yet.  While it apperently has a relationship with the FISH test, it seems to be a newer effort to help narrow down the cases that are the most likely (statistically) to re-occur.  

      http://skinmelanoma.com/health-care-professionals/prospective-clinical-validation/

      http://skinmelanoma.com/health-care-professionals/potential-clinical-benefits/

      Potential Clinical Benefits

      Knowing which Stage I and II patients are at high risk should significantly impact management of their disease

      The AJCC prognostic criteria are the traditional standard for staging cutaneous melanoma (Balch, CM, et. al., Melanoma of the Skin, 2009). However, histopathologic techniques alone do not optimally identify patients at high risk for metastasis. For instance, while Stage I melanomas are considered low risk as a group, some patients do metastasize and are at high risk for metastasis (Balch, 2009).

      There is also poor accuracy for predicting those Stage II patients at high risk for metastasis. Under the current staging system, the 5-year survival rate for clinical Stage II subjects is 53-82%, which overlaps significantly with the survival rate of 22-68% for Stage III cases (Balch, CM, et. al., 2009, 2010). In fact, Stage IIB and IIC patients have a worse 5-year survival rate than stage IIIA patients. These data indicate that there are a significant number of Stage II patients that are not accurately diagnosed as high risk using the current prognostic tools.

      Sentinel lymph node status has been reported as the most accurate prognostic factor for metastatic activity and survival (Gershenwald, JE, et. al., 1999; Morton, DL, et. al., 2006). However, of the 60,000 patients diagnosed with Stage I or II disease last year, up to 8,500 will develop distant metastatic disease within five years of diagnosis (Kalady, MF, et. al., 2003).

      The potential impact on clinical management for Stage I or II melanoma is significant given that the 5-year metastasis risk for DecisionDx-Melanoma Class 2 melanoma is greater than that of AJCC Stage III melanoma. For example, Class 2 patients may benefit from referral to a surgeon or oncologist for consideration of higher intensity monitoring, repeat lymph node mapping, lymph node dissection, adjuvant treatment and clinical trials.

      Also, while it is not often the urgent focus of oncology management discussions, the impact of the relatively good news of receiving a Class 1, low-risk designation should not be underestimated.

      JC
      Participant

      I do not think it is yet clinically available.  Even if it is, these results would not apply to certain subsets–for instance, a microinvasive very thin stage I tumor–that is, one could not generalize a "Bad" prognosis from their dataset of typical stage I or II tumors onto this subset, and, importantly, there is no data on whether treatments (esp after a couple years) would alter the outcome.

      JC
      Participant

      I do not think it is yet clinically available.  Even if it is, these results would not apply to certain subsets–for instance, a microinvasive very thin stage I tumor–that is, one could not generalize a "Bad" prognosis from their dataset of typical stage I or II tumors onto this subset, and, importantly, there is no data on whether treatments (esp after a couple years) would alter the outcome.

      JC
      Participant

      I do not think it is yet clinically available.  Even if it is, these results would not apply to certain subsets–for instance, a microinvasive very thin stage I tumor–that is, one could not generalize a "Bad" prognosis from their dataset of typical stage I or II tumors onto this subset, and, importantly, there is no data on whether treatments (esp after a couple years) would alter the outcome.

      Janner
      Participant

      I think this test is most often used to distinguish Spitz nevi from melanoma.  Spitz nevi are entirely benign and most often found on young individuals.  It looks almost identical to melanoma under the microscope.  So if a pathologist can't make the determination  of Spitz vs melanoma, the FISH test analyzes markers.  Lots of irregular gene findings means melanoma.  Normal gene findings means Spitz nevi.  I could be wrong, but I think this is most likely the major application of this test.

      Janner
      Participant

      I think this test is most often used to distinguish Spitz nevi from melanoma.  Spitz nevi are entirely benign and most often found on young individuals.  It looks almost identical to melanoma under the microscope.  So if a pathologist can't make the determination  of Spitz vs melanoma, the FISH test analyzes markers.  Lots of irregular gene findings means melanoma.  Normal gene findings means Spitz nevi.  I could be wrong, but I think this is most likely the major application of this test.

      JC
      Participant

      if it's just distinguishing spitz nevi from melanoma, then what's the "Kaplan-Meier analysis for 5-year metastasis free survival rates were 98% for Class 1 (low risk) and 37% for Class 2 (high risk)" referring to? 

      JC
      Participant

      if it's just distinguishing spitz nevi from melanoma, then what's the "Kaplan-Meier analysis for 5-year metastasis free survival rates were 98% for Class 1 (low risk) and 37% for Class 2 (high risk)" referring to? 

      Janner
      Participant

      If you read the actual paper and not the press release, it says they are determining a diagnosis between melanoma/spitz or atypical/melanoma and more.

      In all cases, preliminary diagnoses were rendered before sending a tissue for FISH analysis. In most cases, the histologic differential diagnosis was between Spitz nevus and spitzoid melanoma or between atypical nevus (such as variants of deep penetrating/clonal/inverted type-A nevus, pigmented spindle cell nevus, atypical genital nevus, atypical conjunctival nevus showing cytologic atypia, mitotic activity, limited maturation, or proliferative nodules, among others) and nevoid melanoma (Table 1). In some cases, diagnostic considerations included dysplastic nevus and superficial spreading melanoma. In 2 cases, FISH was performed to confirm a suspected but histologically challenging diagnosis of nonsarcomatoid desmoplastic melanoma. At the time of preliminary diagnosis, based on histologic features, each lesion was designated as likely representing an atypical nevus (favoring a benign type), a truly borderline lesion, or a melanoma. These designations reflect the most likely interpretation if FISH was not performed.

      I picked this little sentence out later, which basically sums most of it up for me:

      Obviously, a FISH test is not needed for histologically unequivocal cases. The only current justification for use of this expensive test in a diagnostic setting is to employ it as a diagnostic adjunct to help classify histologically ambiguous lesions.

      I don't have time at the moment to go back and read the hype, but I think the actual study does a good job of describing the purpose and usage for this test.

      http://www.archivesofpathology.org/doi/full/10.5858/arpa.2011-0673-OA

      Janner
      Participant

      If you read the actual paper and not the press release, it says they are determining a diagnosis between melanoma/spitz or atypical/melanoma and more.

      In all cases, preliminary diagnoses were rendered before sending a tissue for FISH analysis. In most cases, the histologic differential diagnosis was between Spitz nevus and spitzoid melanoma or between atypical nevus (such as variants of deep penetrating/clonal/inverted type-A nevus, pigmented spindle cell nevus, atypical genital nevus, atypical conjunctival nevus showing cytologic atypia, mitotic activity, limited maturation, or proliferative nodules, among others) and nevoid melanoma (Table 1). In some cases, diagnostic considerations included dysplastic nevus and superficial spreading melanoma. In 2 cases, FISH was performed to confirm a suspected but histologically challenging diagnosis of nonsarcomatoid desmoplastic melanoma. At the time of preliminary diagnosis, based on histologic features, each lesion was designated as likely representing an atypical nevus (favoring a benign type), a truly borderline lesion, or a melanoma. These designations reflect the most likely interpretation if FISH was not performed.

      I picked this little sentence out later, which basically sums most of it up for me:

      Obviously, a FISH test is not needed for histologically unequivocal cases. The only current justification for use of this expensive test in a diagnostic setting is to employ it as a diagnostic adjunct to help classify histologically ambiguous lesions.

      I don't have time at the moment to go back and read the hype, but I think the actual study does a good job of describing the purpose and usage for this test.

      http://www.archivesofpathology.org/doi/full/10.5858/arpa.2011-0673-OA

      POW
      Participant

      If you look at the original scientific papers, you will see that the authors did a "retrospective" study. They collected OLD biopsy specimens in parafin (for microscopic analysis) and did their test. When they did the FISH test on "ambiguous" specimens (i.e., the original pathology could not say for sure), if the FISH test was strongly positive and then they looked at the patients' historical records, those patients turned out to have no evidence of melanoma in later years. When the FISH test on the ambiguous specimens was negative, those patients turned out not to have melanoma in later years. Therefore, the authors decided to designate FISH negative as "low risk" and FISH positive as "high risk". Confusing, I know.

      POW
      Participant

      If you look at the original scientific papers, you will see that the authors did a "retrospective" study. They collected OLD biopsy specimens in parafin (for microscopic analysis) and did their test. When they did the FISH test on "ambiguous" specimens (i.e., the original pathology could not say for sure), if the FISH test was strongly positive and then they looked at the patients' historical records, those patients turned out to have no evidence of melanoma in later years. When the FISH test on the ambiguous specimens was negative, those patients turned out not to have melanoma in later years. Therefore, the authors decided to designate FISH negative as "low risk" and FISH positive as "high risk". Confusing, I know.

      POW
      Participant

      Oops! I mis-typed. Positive FISH = later melanoma; negative FISH=no later melanoma on AMBIGUOUS specimens only.

      But Janner said it better (above) so ignore everything I said, anyway.

      POW
      Participant

      Oops! I mis-typed. Positive FISH = later melanoma; negative FISH=no later melanoma on AMBIGUOUS specimens only.

      But Janner said it better (above) so ignore everything I said, anyway.

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