Thursday, May 15, 2008

A Bright Spot in Melanoma Care

Last night, representatives from See A Cure attended the 2008 Spring Symposium: Advanced Treatment of Melanoma Follow-up Guidelines by Disease Stage. The title artlessly but accurately summed up the evening’s theme.

About 75 people attended the 3-hour event that was billed as “an evening of education, discussion and connection for patients, survivors, families and friends” and hosted by the Melanoma Foundation of New England (MFNE) on the Dana-Farber Cancer Institute campus.

Skin cancer advocacy groups are well organized, vocal and can be a model to uveal melanoma advocacy efforts. And although cutaneous melanoma and uveal melanoma (an eye cancer also known as choroidal melanoma, eye melanoma, intraocular melanoma and ciliary body melanoma) are not the same disease, the diagnosing, staging, follow-up testing, research and clinical trials are similar for both patient populations.

The most important overlap between skin and uveal melanoma patients is that there are few treatment options for metastatic disease. In fact, uveal patients receive treatment for metastatic disease that is designed for metastatic skin melanoma patients.

Here’s a recap of the evening.

Skin melanoma has ABCDE; uveal melanoma has TFSOM. Acronyms or mnemonics are effective ways to convey a complicated message. MFNE passed out wallet-sized guides to ID’ing skin cancer. A magnet would be a more visible tool.

Skin cancer screening ad: "See Spot. See Spot Grow. See Dermatologist"; uveal needs eye-catching graphics, slogans and ads. Skin has the Ugly Duckling Theory which is to look for suspicious skin nevi within groupings of normal mole/lesions. There are visibility and asymptomatic challenges to “seeing” uveal melanoma. We need to brainstorm solutions.

Tanning beds: Tanning bed UVA rays (vs. UVB) are deeply penetrating. Use of the beds may be cause of higher epidemiological rates (number of cases) and contributing to later development of deadlier disease. MFNE is organizing students to sign a "No Tanning Pledge." Uveal melanoma has no proven link to early sun exposure. However, there may be opportunities for 20-year olds + outreach through well-vision checks.

Tanning Bed Bill – Public Act 1329, is in the Public Health Committee. MFNE is orgainizing outreach to legislators. Uveal can promote legislation on many issues which will be addressed in an upcoming article.

Dr. Marie-France Demierren spoke on "Follow-up Guidelines for Non-Invasive Melanoma." In situ (contained) cancer is always better than invasive cancer. Skin cancer with vertical growth invades beyond the epidermis; uveal melanoma with vertical growth (tumors over 5mm high) break through the Bruch’s membrane with potential extraocular extension which allows both blood and lymph invasiveness.

Skin melanoma uses the LDH serum blood test as a prognostic marker; so does uveal. Depending on grade (Stage I or IV), skin melanoma is treated by primary dermatologist and then a medical oncologist. Uveal patients are typically only seen by their ocular oncologist or retinal specialist. However, medium and large uveal melanoma patients should consider follow-up by a medical oncologist (see page 11) such as Dr. Hodi, Dr. Sato, Dr. Weber, Dr. Atkins among others.

There’s info and then there’s actionable info according to symposium presenter, Dr. Michael Atkins. Early detection will lead to better treatment outcome is true for primary tumors but not metastatic ones; same rule applies to uveal which is why ocular oncologists differ on testing protocols. Mets disease can be detected 45-75% of the time through physical exam and history, imaging only 10% and blood tests 5% of the time.

* Blood test have low sensitivity to disease until tumor burden already detectable through other means such as physical exam and feeling of lymph nodes; same is true in uveal. Europe is screening with the S100B – a sensitive blood test not routinely available in US and of no prognostic value in uveal. MIA (Melanoma Inhibitory Activity) and RT-PCR clinical tests that are not validated, yet; unclear benefit to uveal.

* A normal scan does not mean no evidence of disease (NED); it means there is no measurable disease (if any). Treatment is based on measurable disease and mets may be present if not always measurable.

* Adjuvant therapies (preventative care) are not given in either skin or uveal since no benefit shown when given for metastatic disease (same drugs used in adjuvant as in mets).

* The median time to relapse is inversely related to disease stage of primary tumors for both skin and uveal melanoma (smaller tumors 6+ years; larger tumors, 2-3 years). Overall risk lessens over time for skin melanoma; is not true for uveal where threat of mets is lifelong due to long latency period.

Metastatic Treatment
Chemotherapy: DTIC chemo been around 30 years. Works but not as long or as well as expected.
Immunotherapy: IL-2 been around since 1998 (from data compiled between 1986-1994). No better than chemo.
Combination: Both DTIC/IL-2 are effective but are toxic, inpatient, expensive and limited treatment locations (not avail at Dana-Farber). Response is better, relapse takes longer, but survival benefit is nominal.
Molecular Targeted Therapy: CTLA-4 antibodies such as Ipilimumab and Tremelimumab fight tumor-induced immune suppression. C-kit by Dr. Hodi is a promising treatment. Challenge is that there are 20 or more subsets of skin melanomas that are molecularly different; uveal melanoma is fairly homogeneous suggesting single-agent treatment but research continues. Meantime, uveal mets patients receive skin melanoma therapies.

Clinical trials: Debate over whether the treatment is better or the patient selection is better. Promising results from Phase I and II trials are not repeated in larger Phase III trials which suggests bias in patient selection in the smaller trials.

Outcome Measurements:
Between 1975-2003 skin melanoma mortality rose 35% while prostate, breast, colon and cervical all dropped 50%, 10%, 25% and 10% respectively; uveal melanoma mortality remains unchanged for over 25 years despite treatment advances.

Just 3-4 minutes of sun exposure are needed to get daily allowance of Vitamin D. Can get through supplements, too. SPF lotions must be applied 15-20 before sun exposure in order to provide maximum protection.

MFNE did an excellent job providing information to the lay public - both patient and general interest - on skin melanoma issues. Their work can be a model for uveal melanoma organizational efforts.

It’s your sight.

It’s your life.

Together, we can see a cure.™

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