First follow-up appointment after CAPOX for ex-goblet cell adenocarcinoma of the appendix (GCC) and a RUN!!!

Yesterday was my first follow-up appointment with my oncologist after completing (in my own special way, full deets in prior posts) the 4 rounds of oxaliplatin and capecitibine in the past 3 months prescribed as adjuvant for my Stage II GCC.  Whew!  In so many ways!

It was pretty non-eventful as expected.  Here's my self report:  My feet still burn quite a lot.  Although I no longer feel like I am walking in over-sized clown shoes!  My fingers are still pretty numb at the tips but I can type, pick up pins and deal with other fine motor skills much better than previously.  The area of the IV infiltration to my right forearm is still red, weird and tender - but improving since B had the genius idea of putting a moderate strength steroid cream on it twice daily.  It is no longer waking me with pain when I accidentally smush it in my sleep!  I have been dealing with pretty significant joint pain, particularly to ankles, knees and hips since the very start of treatment and they are still hanging around with a vengeance!  The brown splotchy lesions I developed are gradually resolving.  Oddly, patches of vitiligo that I began to develop in my Opdivo trial are increasing.  So, weird.  BUT!  My abdominal pain is gone!!  I can eat pretty much what I want though I am taking that adventure slowly and still taking my pepcid.  Currently, salads, citrus fruit, and apples with peels are back on the menu! FYI (with a TMI warning!!) ~ After surviving 2 months of liquid poopage every 2 hours round the clock following surgery to remove my appendix and right 1/3 of my colon, succeeded by obstruction and a second surgery, and all sorts of crazy poopage problems while on CAPOX with at least 4-6 loose stools on the good days, things are much better!  Stooling is not "normal" with 2-3 loose stools per day combined with some urgency ~ when you gotta go - you gotta go!!!  Still, if you are facing this sort of colon removal, it is a manageable process!

Anyhow, the main point of my recheck was to determine a plan for long term follow-up.  B rechecked with the docs I consulted at Vanderbilt, not to mention all the papers and peeps knowledgeable about GCC.   We went over their points and her own perspective with my local oncologist.  In the end, we determined that I will have my first follow-up scan (a low dose CT without contrast of the chest and regular CT with and without contrast of the abdomen and pelvis) at the end of March.  Future scans are planned to be a CT without contrast of the chest combined with a CT of abd/pelvis WITH contrast only, in order to keep continued radiation exposure to a minimum.  The consensus is to have your first scans 6 months after diagnosis and then annually.  Additionally, I will be seeing the oncologist and having lab work, to include a "CEA" level, every 3 months.  What is "CEA"?  Carcinoembryonic antigen is a protein in your blood that is normally very high in a fetus, but is usually low in healthy adults. It can be elevated in those adults should there be a growing thyroid, lung, breast, ovarian, pancreatic, stomach, bladder, colon, or rectal cancer.  As you see from the list, GCC is NOT included.  We are rolling with this test due to its usefulness in colon cancer which may, or may not, match up with my cancer. In fact, when it was drawn in the hospital just after having said cancer, my levels were normal.  But, we'll try it.  B is also researching other tests we may add to the mix.  How long will this go on?  The end point was not conclusively determined, but will likely be somewhere between 3-5 years.  All peeps interviewed agreed that we are at the point in my melanoma ta-dah (16 years overall, 9 years Stage IV and over 8 NED) that I am no longer in need of scans in that department.  Obviously, additional studies would be ordered should I develop untoward symptoms or demonstrate adverse numbers in my lab values.

In the spirit of upward and onward, combined with a break in the cold rainy weather that has been a bit perpetual lately,  B and I have done some "structural" work on our garden (taking out some saplings and overhanging tree branches, pruning overgrown roses, crepe myrtles, fruit trees, and rhodies) as well as taking down some netting/fencing that prevented the intrusion of rabbits and deer not at all!  I have continued to increase my indoor work-outs moving from 10 minutes to 15 on the elliptical as well as upping the 'level' from 3 to 4!  I am doing more sit-ups, push-ups, planks and reps with my weights.  But, the coup de grace to call an end to my incarceration is this:  I completed my first run since August!  It was more of a slog.  Only a mile.  But, I did it!!! 

Pre run!

On my return!!!  None the worse for wear.  With photos from my ever watchful Medical Meerkat Photog!

It is not always easy, but in the words of wise dear Jeanne, "Life is good!" - love, les

More evidence that Vitamin D matters for melanoma and cancer patients generally!

Not news, really.  Here are a zillion related posts!!!
2014:  Vitamin D and Melanoma 
2016:  Vit D and melanoma - Part 2 
Jan 2017:  Vitamin D - low levels associated with a worse prognosis in melanoma...again... 
June 2017:  Vitamin D and melanoma - folks with higher levesl do better - again!!! 
September 2017:  Vitamin D and melanoma

Now this:

Circulating 25-hydroxyvitamin D up to 3 decades prior to diagnosis in relation to overall and organ-specific cancer survival.  Weinstein, Mondul, Yu, et al.  Eur J Epidemiol. 2018 Aug 2.

While vitamin D has been associated with improved overall cancer survival in some investigations, few have prospectively evaluated organ-specific survival. We examined the accepted biomarker of vitamin D status, serum 25-hydroxyvitamin D [25(OH)D], and cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Of 4616 cancer cases with measured serum 25(OH)D, 2884 died of their cancer during 28 years of follow-up and 1732 survived or died of other causes. Proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between pre-diagnostic 25(OH)D and overall and site-specific survival. Serum 25(OH)D was significantly lower among cases who subsequently died from their malignancy compared with those who did not (medians 34.7 vs. 36.5 nmol/L, respectively). Higher 25(OH)D was associated with lower overall cancer mortality. Higher 25(OH)D was related to lower mortality from the following site-specific malignancies: prostate, kidney, and melanoma, but increased mortality from lung cancer. Improved survival was also suggested for head and neck, gastric, pancreatic, and liver cancers, though not statistically significantly, and case numbers for the latter two organ sites were small. Higher 25(OH)D status years prior to diagnosis was related to improved survival for overall and some site-specific cancers, associations that should be examined in other prospective populations that include women and other racial-ethnic groups.

For what it's worth.  - c

HAPPY NEW YEAR!!!!!!!!!!!! (And ~ CAPOX as adjuvant for ex-goblet cell adenocarcinoma of the appendix = DONE!)

Happy 2019, my dear peeps!!!

The past 4 months have been a crazy, horrible nightmare, in so many ways.  As I noted here, on day 5 (12/21) of round 4, this one with capecitibine alone, my oxaliplatin having been held due to my neuropathies, abdominal pain and misery were in full force.  For five days I did nothing but move excruciatingly slowly and carefully - as anything jarring or touching my abdomen (like my own arm!!!) produced even more pain - from bed, to chair, to couch; managing that only by virtue of B's assistance and lots and lots of marinol!!  By Wednesday (12/26) my abdomen was still swollen and tender, but less so and I was able to putter about the house a little.  We held the capecitibine all that time as my colitis was too severe to handle more.  Once I was better we discussed attempting more doses, finally deciding I was done.  That was all I could stand.  The whole CAPOX tadah was pretty hellish!!!  BUT!  The most important word in that sentence is ~ WAS!!!!!!!!!!!  I AM DONE!!!!  It has been one heck of an experience!  Hopefully, it did me some good.  Lord knows, if side effects are a positive indication, I should be good to go!!!  I will see my oncologist on the 7th and develop a follow-up plan of some sort.  There is my Stage IV melanoma status to be considered.  B is concerned about all the radiation I have been exposed to with CT scans of my neck, chest, abdomen and pelvis every 3 months for the years of my trial followed by years of them every 6 months and then annually for a couple more.  And that's not even counting various PET scans, chest x-rays, and CT scans I had from 2003 to 2010 or the ones I had while hospitalized in August!  We'll see what we figure out.

I was finally able to get back on the elliptical 4 days ago for my big 15 minutes.  And today ~ I worked in my yard!!!  Though I will certainly be sore tomorrow, it was glorious!  I was able to breathe the fresh air and imagine all the beauty that spring will bring.  I still have some numbness in my fingers and hands.  My feet are burning as I type.  The nasty red painful area remains on my right forearm where the last oxaliplatin infusion infiltrated on 12/3, though it is slowly getting better.  The residual neuropathies should gradually resolve as well.

My dear peeps from near and far, pulled me through - again!!  ALL of YOU, are the reason I am here!  I have been blessed with physical and emotional support that I will NEVER be able to repay or even fully express my gratitude for.  I have been lifted up when I could not - literally (Ruthie and Bentie!!!) and emotionally by ever so many.  Kind words via cards, texts, phone calls, emails and on message boards.  Sweetness that spoiled me in all sorts of ways ~ supportive visits, inspiring books, helpful salves, anti-nausea ginger chews, beautiful talismans, playful gadgets, bright red buttons, funny distractions, meals on wheels, warm slippers, beauty in ever so many forms!  I am blessed.  I appreciate each and every one of you  more than you will ever know.

Together we've made it to 2019!  As for me, I will march forward WITH my past.  All of it.  The difficult and the beautiful.  Working to regain my strength.  Doing my best to appreciate what each day brings.  Striving to make my time on this spinning ball worth something.  Enjoying the wonder of it all.  Appreciating all of you.

For all my dear sweet peeps, may this year bring much joy, love, peace and adventure.  Much love, les

Mucosal melanoma - a couple of reports

Melanoma sucks.  Mucosal melanoma sucks even more.  Here are some prior posts:

Mucosal melanoma - abstracts from 2016 to now

Here is an abstract regarding the use of pembro and a case report in which a topical anti-fungal was used in a patient with vaginal melanoma (although radiation to a brain met and nivo was started as well....so it's a bit muddy!!!) to good effect.  For what they're worth:

Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006. Hamid, Robert, Ribas, Hodi, et al.Br J Cancer. 2018 Sep 11.

Mucosal melanoma is an aggressive melanoma with poor prognosis. We assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in KEYNOTE-001 (NCT01295827), -002 (NCT01704287), and -006 (NCT01866319).

Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or Q3W. Response was assessed by independent central review per RECIST v1.1.

1567 patients were treated and 84 (5%) had mucosal melanoma. Fifty-one of 84 were ipilimumab-naive. In patients with mucosal melanoma, the objective response rate (ORR) was 19% (11-29%), with median duration of response (DOR) of 27.6 months (range 1.1 + to 27.6). Median progression-free survival (PFS) was 2.8 months (2.7-2.8), with median overall survival (OS) of 11.3 months (7.7-16.6). ORR was 22% (11-35%) and 15% (5-32%) in ipilimumab-naive and ipilimumab-treated patients.

Pembrolizumab provides durable antitumour activity in patients with advanced mucosal melanoma regardless of prior ipilimumab.

Itraconazole treatment of primary malignant melanoma of the vagina evaluated using positron emission tomography and tissue cDNA microarray: a case report.  Inoew, Tsubamoto, Isono-Nakata, et al.  BMC Cancer. 2018 Jun 4.

Primary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial.

A 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and ¹⁸F-fluoro-deoxyglucose positron emission tomography (FDG/PET)-computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET-CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months.

The findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.

Wishing you all my best. - c

CheckMate 067 - 4 year outcomes for nivo/ipi combo vs nivo alone in melanoma patients

I have been following the data (and contributing to some) around immunotherapy for over 8 years!  So of course I've followed the CheckMate 067 trial.  Here are just a few early reports:   CheckMate 067 - ipi/nivo combo

Now, this ~

Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Hodi, Chiarion-Sileni, Gonzalez, et al. Lancet Oncol. 2018 Oct 18.  

Previously reported results from the phase 3 CheckMate 067 trial showed a significant improvement in objective responses, progression-free survival, and overall survival with nivolumab plus ipilimumab or nivolumab alone compared with ipilimumab alone in patients with advanced melanoma. The aim of this report is to provide 4-year updated efficacy and safety data from this study.  

In this phase 3 trial, eligible patients were ... previously untreated, unresectable, stage III or stage IV melanoma, known BRAF^V600 mutation status, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned 1:1:1 to receive intravenous nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks, or nivolumab 3 mg/kg every 2 weeks plus placebo, or ipilimumab 3 mg/kg every 3 weeks for four doses plus placebo. Randomisation was done via an interactive voice response system with a permuted block schedule (block size of six) and stratification by PD-L1 status, BRAF mutation status, and metastasis stage. The patients, investigators, study site staff, and study funder were masked to the study drug administered. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done on the intention-to-treat population, whereas safety was assessed in all patients who received at least one dose of study drug. The results presented in this report reflect the 4-year update of the ongoing study with a database lock date of May 10, 2018. This study is registered with ClinicalTrials.gov, number NCT01844505.  

Between July 3, 2013, and March 31, 2014, 945 patients were enrolled and randomly assigned to nivolumab plus ipilimumab (n=314), nivolumab (n=316), or ipilimumab (n=315). Median follow-up was 46·9 months (IQR 10·9-51·8) in the nivolumab plus ipilimumab group, 36·0 months (10·5-51·4) in the nivolumab group, and 18·6 months (7·6-49·5) in the ipilimumab group. At a minimum follow-up of 48 months from the date that the final patient was enrolled and randomised, median overall survival was not reached (38·2-not reached) in the nivolumab plus ipilimumab group, 36·9 months (28·3-not reached) in the nivolumab group, and 19·9 months (16·9-24·6) in the ipilimumab group. The hazard ratio for death for the combination versus ipilimumab was 0·54 and for nivolumab versus ipilimumab was 0·65. Median progression-free survival was 11·5 months (95% CI 8·7-19·3) in the nivolumab plus ipilimumab group, 6·9 months (5·1-10·2) in the nivolumab group, and 2·9 months (2·8-3·2) in the ipilimumab group. The hazard ratio for progression-free survival for the combination versus ipilimumab was 0·42 and for nivolumab versus ipilimumab was 0·53. Treatment-related grade 3-4 adverse events were reported in 185 (59%) of 313 patients who received nivolumab plus ipilimumab, 70 (22%) of 313 who received nivolumab, and 86 (28%) of 311 who received ipilimumab. The most common treatment-related grade 3 adverse events were diarrhoea in the nivolumab plus ipilimumab group (29 [9%] of 313) and in the nivolumab group (nine [3%] of 313) and colitis in the ipilimumab group (23 [7%] of 311); the most common grade 4 adverse event in all three groups was increased lipase (15 [5%] of 313 in the combination group, ten [3%] of 313 in the nivolumab group, and four [1%] of 311 in the ipilimumab group). Serious adverse events were not analysed for the 4-year follow-up. In total for the study, there were four treatment-related deaths: two in the nivolumab plus ipilimumab group (one cardiomyopathy and one liver necrosis), one in the nivolumab group (neutropenia), and one in the ipilimumab group (colon perforation). No additional treatment-related deaths have occurred since the previous (3-year) analysis.

The results of this analysis at 4 years of follow-up show that a durable, sustained survival benefit can be achieved with first-line nivolumab plus ipilimumab or nivolumab alone in patients with advanced melanoma.

At this point, these results are not surprising.  The ipi/nivo group median overall survival was not reached at 38 months, not reached for nivo alone at 36 months, and was 19 months in the ipi only group.  Side effects greatest with 59% of patients experiencing them with ipi/nivo, experienced by 22% taking nivo alone, and by 28% on ipi as a single agent.  The most common grade 3 side effect was diarrhea/colitis.  The most common grade 4 side effects was increased lipase.

Thanks, ratties!!! May we all continue to beat our assigned expiration dates!!! - c

Important stuff floating in our blood - tumor DNA, micro RNA, cytokines - can determine tumor burden, predict response, and side effects for melanoma patients!!!

Continuing from yesterday.....  Our blood is a fairly accessible information rich soup that can tell us all sorts of things about our bodies!!!  One important ingredient for melanoma patients is circulating tumor DNA.  Here's a load of prior reports: Circulating tumor DNA - to determine diagnosis, disease burden, response to therapy, etc  Here are a couple more reports:

Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients.  McEvoy, Warburton, Al-Ogaili, et al. BMC Cancer. 2018 Jul 9.

Circulating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients' overall metabolic tumour burden (MTB).  Thirty-two treatment naïve metastatic melanoma patients were included in the study. MTB and metabolic tumour volume (MTV) was measured by 18F-fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT). Plasma ctDNA was quantified using droplet digital PCR (ddPCR).  CtDNA was detected in 23 of 32 patients. Overall, a significant correlation was observed between ctDNA levels and MTB. CtDNA was not detectable in patients with an MTB of greater than/= to 10, defining this value as the lower limit of tumour burden that can be detected through ctDNA analysis by ddPCR.  We showed that ctDNA levels measured by ddPCR correlate with MTB in treatment naïve metastatic melanoma patients and observed a limit in tumour size for which ctDNA cannot be detected in blood. Nevertheless, our findings support the use of ctDNA as a non-invasive complementary modality to functional imaging for monitoring tumour burden.

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real-world setting. Rose, Luber, Makell, et al. Mol Oncol. 2018 Aug 16.

Melanoma currently lacks a reliable blood-based biomarker of disease activity, although circulating tumor DNA (ctDNA) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ctDNA in patients with metastatic or high-risk resected melanoma. Patients were prospectively accrued into greater than/= to 1 of 3 cohorts, as follows. Cohort A: patients with radiographically-measurable metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing digital PCR assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ctDNA data. Cohorts B and C: patients with BRAF- or NRAS-mutant melanoma who had either undergone surgical resection of high-risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C). Patients were followed longitudinally with serial ctDNA measurements with contemporaneous radiographic imaging to ascertain times to detection of disease activity and progressive disease, respectively. The sensitivity and specificity of the ctDNA assay was 86.8% and 100%, respectively. Higher tumor burden and visceral metastases were found to be associated with detectable ctDNA. In 2 patients in cohort A, ctDNA test results revealed a targetable mutation where tumor testing had not; both patients experienced a partial response to targeted therapy. In 4 of 30 patients with advanced melanoma, ctDNA assessments indicated evidence of melanoma activity that predicted radiographic evidence of disease progression by 8, 14, 25 and 38 weeks, respectively. CtDNA was detectable in 3 of these 4 patients coincident with radiographic evaluations that alone were interpreted as showing no evidence of neoplastic disease. Our findings provide evidence for the clinical utility of integrating ctDNA data in managing patients with melanoma in a real-world setting.

Among the many bio-markers present in our blood, there's also circulating RNA.   Prior reports:  RNA and biomarkers generally  Now, this:

Extracellular microvesicle microRNAs as predictive biomarkers for targeted therapy in metastastic cutaneous malignant melanoma.  Svedman, Loncharoenkal, Bottaj, et al. PLoS One. 2018 Nov.

Mitogen activated-protein kinase pathway inhibitors (MAPKis) improve treatment outcome in patients with disseminated BRAFV600 mutant cutaneous malignant melanoma (CMM) but responses are of limited duration due to emerging resistance. Although extensive research in mechanisms of resistance is being performed, predictive biomarkers for durable responses are still lacking. We used miRNA qPCR to investigate if different levels of extracellular microvesicle microRNA (EV miRNA) in matched plasma samples collected from patients with metastatic IV BRAFV600 mutated CMM before, during and after therapy with MAPKis could serve as predictive biomarkers.  EV miRNAs were extracted from plasma samples from 28 patients collected before and during therapy, measured by quantitative PCR-array and correlated to therapy outcome. Increased levels of EV let-7g-5p during treatment compared to before treatment were associated with better disease control with MAPKis. Elevated levels of EV miR-497-5p during therapy were associated with prolonged progression free survival (PFS).  EV miRNAs let-7g-5p and miR-497-5p were identified as putative novel predictive biomarkers of MAPKi treatment benefit in metastatic CMM patients highlighting the potential relevance of assessing EV miRNA during and after treatment to unravel novel mechanisms of resistance.

Circulating cytokines are substances like interleukin, interferon, and growth factors, that cells in our immune system secrete in order to affect other cells. Here's a report for a little background:  Eosinophilia with Nivo and Pembro - A predictor of success?!!
Here they are being examined as predictors of toxicity to immunotherapy:

Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy. Lim, Lee, Gide, et al. Clin Cancer Res. 2018 Nov 8.  

Combination PD-1 and CTLA-4 inhibitor therapy has dramatically improved the survival of patients with advanced melanoma but is also associated with significant immune-related toxicities. This study sought to identify circulating cytokine biomarkers of treatment response and immune-related toxicity.  The expression of 65 cytokines was profiled longitudinally in 98 melanoma patients treated with PD-1 inhibitors, alone or in combination with anti-CTLA-4, and in an independent validation cohort of 49 patients treated with combination anti-PD-1 and anti-CTLA-4. Cytokine expression was correlated with RECIST response and immune-related toxicity, defined as toxicity that warranted permanent discontinuation of treatment and administration of high dose steroids.

Eleven cytokines were significantly upregulated in patients with severe immune-related toxicities at baseline and early during treatment. The expression of these eleven cytokines was integrated into a single toxicity score, the CYTOX score, and the predictive utility of this score was confirmed in the discovery and validation cohorts. 

The CYTOX score is predictive of severe immune-related toxicity in melanoma patients treated with combination anti-CTLA-4 and anti-PD-1 immunotherapy. This score, which includes pro-inflammatory cytokines such as IL-1a, IL-2 and IFNa2, may help in the early management of severe, potentially life-threatening immune-related toxicity.

Hoping for much more consistency and use of these relatively simple tests in order to reap better treatment outcomes for melanoma patients in 2019!!! - c

Pretreatment NLR levels prognostic in melanoma patients!

As noted in the discussion of adjuvant treatment by melanoma Big Dogs, biomarkers will no doubt come to play an important role in diagnosis and treatment management for melanoma patients.  I've reported on simple, easy to attain and run blood values to provide prognostic and response information for melanoma patients for a looooong time.  Collection of blood for the measurement and comparison of the quantity of white blood cells is just one.  Here are lots of reports:  Prior reports on neutrophils

Now there's this:

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in melanoma patients:  A meta-analysis.  Zhan, Ma, Jian.  Clin Chim Acta. 2018 May 20.

Recently, the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) has been widely evaluated in many cancers. Here we assessed the prognostic value of pretreatment NLR in melanoma.  A range of online databases was systematically searched up to March, 2018 for identify available studies which assessed the prognostic significance of NLR. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) were weighted by generic inverse-variance and pooled in random effects meta-analysis.

Twelve studies with 4593 individuals were included. Patients with elevated NLR had a significantly shorter overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS). Subgroup analyses showed that the negative prognostic effect of elevated NLR on OS remained substantial in North American and European populations and patients with non-metastatic and metastatic stage. Additionally, elevated NLR was related to worse OS in patients with melanoma, regardless of the sample size and the cut-off value.

Our findings suggest that elevated pretreatment NLR was associated with poor prognosis in melanoma patients, suggesting NLR might be a prognostic factor in patients with melanoma.

And again...

Neutrophil to lymphocyte ratio is an independent predictor of outcome for patients undergoing definitive resection for stage IV melanoma. Kanatsios, Melanoma Project, Li Wai Suen, et al. J Surg Oncol. 2018 Sep 9.

The aim of this study was to perform a retrospective analysis of survival rates and determine prognostic indicators for patients who underwent definitive surgical resection of stage IV melanoma.

Patients included were those who underwent complete resection of metastatic melanoma. Data was analyzed using IBM SPSS 2.0. Survival estimates were derived from Kaplan-Meier, log-rank, and Breslow tests.
The study population (n = 95) consisted of 60 males and 35 females. Median overall survival (OS) from the first metastasectomy was 49 months (31-67 months). OS at 1, 2, and 5 years was 92%, 87%, and 50% respectively. Predictors of survival included clear surgical margins compared to patients with positive margins (median OS 53 vs 20 months). A preoperative neutrophil to lymphocyte ratio less than 5 experienced a median OS of 65 months compared to 15 months.

This study's results are consistent with previous findings demonstrating favourable long-term outcomes following selective resection of metastatic melanoma. In addition to achieving clear surgical margins, a low preoperative neutrophil to lymphocyte ratio was associated with improved outcomes. These factors may help identify surgical candidates.  (As well as those who may need to more aggressively pursue systemic treatment - adjuvant or other wise. Just my 2 cents!!!)

For what it's worth.  Again. - c