Wednesday, March 21, 2018

In-transit melanoma. Two "new" treatment options!

In-transit mets from melanoma can be very difficult to deal with.  This collection of posts covers treating them with limb perfusion therapy and earlier studies with PV-10:  Studies looking at treating in-transit mets

Now there's this: 

Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod. Fujimura, Kambayashi, Sato, et al.  Case Rep Oncol. 2018 Jan 4.

Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

And this:

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study. Read, Smith, Thomas, et al.J Surg Oncol. 2018 Mar 12.
Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease.

An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions.

Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response.

Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

While the entire report is included in the link above....for comparison there was this in 2017:

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma. Foote, Read, Thomas, et al. J Surg Oncol. 2017 Feb 23. 

Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis. The median follow up duration was 19.25 months. Size of metastases (less than10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events.  

And this from

Intralesional PV-10 for in-transit melanoma-A single-center experience.  Lippey, Bousounis, Behrenbruch, et al.  J Surg Oncol. 2016 May 30. 

Nineteen patients with in-transit melanoma were treated with intralesional PV-10 between 2010 and 2014. Disease control (complete or partial response or disease stability) was achieved in 68% of patients with 26% having a complete response.

Overall, while all these studies look at relatively small numbers, the results are certainly hopeful.  As is usual in melanoma it seems that combining treatments (radiation with intralesionals, immunotherapy with topicals) may boost response even more.  It is a tough road, but ratties are moving us forward bit by bit!  - c

Monday, March 19, 2018

25 - 50% of effective drugs we currently rely upon are derived from plants....

Mother nature wears a coat of many colors!  While I am not about to endorse a "natural" treatment for melanoma just because it sounds sweet with absolutely no supporting data,  I am still the girl who eats more fruits and veggies than most, refuses to prescribe unneeded medications for my little patients, grows her own fruits and flowers, and loves hiking and running through the beauty our natural world provides.  Additionally, in case you think my "Everything cures melanoma!!" posts are sarcastic, uninformed or lacking in hope, I fully realize that 25-50% of all effective, current medications we use are plant based.

Vincristine (Here's a post on that one: Everything cures melanoma - and then there's vincristine!! ), ephedrine, and penicillin are medications that have figured largely in my career as I have worked to take care of my little patients for the past 34 years!!  Here's a tiny historical retrospective, on a few of the drugs you and I (or someone we love) use everyday, based on the MedScape article -  From Folk to pharma:  Natural Remedies that became medications, by Jennifer Leavitt, 10/2/2017:

Cinchona bark, from Peru, led to the development of quinine in Europe in 1640.  It has been essential in treating malaria.  In 1912, it was serendipitously found to be useful in treating arrhythmias as well!

The Greeks, Egyptians, and those in ancient India used mold to treat infections.  In the 1600's, folks in Poland and Russia applied a combo of wet bread and spider webs to wounds to aid healing.  In the 1870's, Sir John Scott Burdon-Sanderson and Joseph Lister noted that cultures contaminated with mold grew no further bacteria.  By 1928, Alexander Fleming, identified the protective mold as Penicillium notatum.  He spent years sending out samples to try to find someone who could mass produce it in a stable form.  In 1938, the isolate was purified and penicillin...the first antibiotic...still essential to human lives today, was developed.

As early as 1785, Digitalis purpura, Foxglove, was used to treat edema and tuberculosis.  Later, it was identified as a treatment for congestive heart failure, leading to the drug digoxin, still an essential drug in the treatment of a-fib and atrial flutter.

Native Americans crushed the needles of the Pacific Yew to use as an anti-inflammatory.  Use had to be carefully managed because the seeds were lethal!  In the 1960's, the cytotoxic properties of these needles were discovered, leading to the isolation of Paclitaxel, which was FDA approved in 1992.  It remains a critical drug in the treatment of breast cancer and Kaposi sarcoma.

Bark from the white willow was used in 400 BC Europe and China to decrease swelling, headache, and fever.  Ancient Egyptians and Assyrians found it a hot commodity in trade.  In 1763 it was found to be effective in treating malaria. Meanwhile....

...Meadow Sweet was used by Celtic and Druid priests in a similar fashion. Later, both meadow sweet and willow bark were found to be sources of Salicylic acid.  Aspirin!!!

Red yeast rice, made by pouring fermented yeast over red rice, was utilized as for its nutritional and medicinal properties for hundreds of years in China.  Later, the combination was found to possess statin-like chemicals.

The American Mandrake, or Mayapple, was first used in the 19th century for its healing powers, especially in the treatment of warts.  In 1835 Dr. John King identified it's compounds and etoposide was created in 1966.  In 1983 the FDA approved this drug for the treatment of cancer - to include lung, Kaposi, testicular, Ewing's, lymphoma, glioblastoma and multiforme cancers.

Poppy leaves and seeds have long been used to aid in rest and sleep.  Opium was isolated in the 19th century leading to the development of codeine and morphine.

The use of ephaedra dates back 5000 years to the treatment of hay fever, colds, and asthma in China!

Camphor was used by the ancients to decrease inflammation and sprains.  It was used in India to treat fever and diarrhea, and with some success in the treatment of cholera in the Naples epidemic of 1854.

And finally, there's good old grain alcohol, used by all sorts of folks for centuries.  In 1831 the inhalation of ether was used for sedation and the use of nitrous oxide in 1844 lead to the development of present day anesthesia.

So, YES!!!  I am a full, wholehearted believer in the power of natural remedies!  I am also a wholehearted believer in the power of snake venom, poison ivy, arsenic, and hemlock.  Man has the power to study and realize the positive and negative effects of all nature's bounty!!!   We would be incredibly foolish to allow the continued loss of acres of rain forest, both for the injury to that individual ecosystem as well as the damage such a loss would inflict on climates across the globe, but  also for the loss of potentially curative plant and animal compounds the bounty of nature has bestowed upon it as well.  (Yes, I am also a huge fan of the film, Medicine Man!  No, not for Sean Connery!!!  For the ants!!!  Okay...and Sean Connery!)

So, Mother Nature ~ Thank you!  Yeah, you gave us the plague and melanoma...but you gave us a lot of other cool stuff, too. I will continue to enjoy your beauty and admire your majesty.  I will also remain a strong advocate for melanoma peeps in real time.  If your bounty will cure us...I will be the first to scream it here and everywhere else I can find an audience.  Until then, I will enjoy your honey and feed your bees with my flowers, blueberries and other pollinator friendly plants.  I will not spray pesticides or harm your critters.  And when we find a cure to melanoma from any of your minions...well, let's just say...the promotion will be HUGE!!! - c

Thursday, March 15, 2018

More shoo shoo! Or...intestinal flora and melanoma

I've posted on all things dietetic and the flora in our gut in particular for YEARS!!!  Here was my latest round-up just this January:  Microbes again...and how they may be associated with improved response to anti-PD-1 for melanoma patients...and you might even laugh!!!

I do recommend healthy eating and exercise.  I do take 2000 iu of vitamin D daily.  I do eat lots of foods with active cultures in them - yogurt, kefir, sauerkraut, etc. I eat them because I like them and we have learned that cooties in our gut are important whether they really do anything when we take anti-PD-1 and deal with melanoma or not.  I wish that making immunotherapy effective for everyone who takes it were as simple as a diet change.  However, as I've noted in prior posts...this pendulum continues to swing back and forth and the data is far from conclusive.

Now, there's this ~

The gut microbiota and immune checkpoint inhibitors. Humphries and Daud.Hum Vaccin Immunother. 2018 Mar 1.

Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.

For what it's worth.  Hang tough.  Be well. - c

Wednesday, March 14, 2018

Sew Chaotically! - Another afghan. "Soft grey and white with story books!"

A dear one of mine shared with me the sweetest news!!!  She's having a little boy this summer!!!  I screeched and danced and asked, "What are you thinking for the nursery?"  "Soft grey and white with a story book theme, " she answered.  I got busy...

I love books, good children's books in particular!!!  So, it was hard for me to choose, but this selection includes three of the top faves of my own children!

All done and ready for cuddles and stories!!  Pretty close on my yarn reckoning, don't you think?  Loving my project bag this same sweet little mama gave me (It was fate that hers be the first project it held!!!) along with the collection of crochet needles and tools Ruthie gave me!  Ready for a new project!!!  Sew chaotically!!! Happy pi day!!!!  - c

Monday, March 12, 2018

BRAF/MEK before surgery as well as after is MUCH better, than just AFTER surgery for melanoma!! Plus trial still recruiting resectable stage III/IV melanoma peeps.

We have long known that BRAF positive melanoma peeps can respond almost magically to BRAF inhibitors, and do even better, with fewer side effects and less tumor work-around, when those medications are combined with a MEK inhibitor.  However, we also know that far too often, despite the combo, tumors can still learn to rear their ugly heads after that initial response.  For that reason, BRAF/MEK inhibition is often used to lower tumor burden quickly, then start the patient on immunotherapy.  Lot's of studies are also looking at pairing this targeted therapy with immunotherapy and a host of other drugs that will boost the durability of these responses.  Here are a zillion BRAF inhibitor related posts:  More than you ever wanted to know about BRAF inhibitors/targeted therapy in melanoma

With all that being noted...the next great way to treat melanoma is through adjuvant care.  Meaning - after the patient is rendered "free of disease" (usually these are Stage III or IV patients whose tumors are removed surgically and/or treated with radiation, whose follow-up scans of the irradiated area show no viable tumor) they can then be treated with immunotherapy or targeted therapy to try to make sure that their melanoma does not come back.  This was the premise of the study arm I was in, taking nivo from 2010-2013.  We know adjuvant care, whether you use ipi, anti-PD-1, or BRAF/MEK, works for many in melanoma!!!  Here are a zillion posts on that:  Adjuvant treatments WORK in melanoma!!!

Now....with all that said...we are also learning about NEOadjuvant treatment.  This treatment is where you find out the patient has melanoma.  THEN you start them on their meds.  THEN you remove the tumor and continue the treatment.  Here are some reports on neoadjuvant studies looking at BRAFi as neoadjuvant, along with the the OpACIN trial which used ipi/nivo as neo-adjuvant for Stage III melanoma patients.  Note:  you will have to scroll through some of the posts as some of the NEO-adjuvants articles are interspersed. - Neoadjuvant studies in melanoma

Researcher Amaria (lead author of the article below), has figured largely in the published data for BRAF/MEK as neoadjuvant.  Now, there's this:

Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Amaria, Prieto, Tetzlaff, et al. Lancet Oncol. 2018 Jan 17.

Dual BRAF and MEK inhibition produces a response in a large number of patients with stage IV BRAF-mutant melanoma. The existing standard of care for patients with clinical stage III melanoma is upfront surgery and consideration for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant targeted therapy with BRAF and MEK inhibitors (such as dabrafenib and trametinib) might provide clinical benefit in this high-risk p opulation.

We undertook this single-centre, open-label, randomised phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible participants were adult patients with histologically or cytologically confirmed surgically resectable clinical stage III or oligometastatic stage IV BRAFV600E or BRAFV600K (ie, Val600Glu or Val600Lys)-mutated melanoma. Eligible patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, a life expectancy of more than 3 years, and no previous exposure to BRAF or MEK inhibitors. Exclusion criteria included metastases to bone, brain, or other sites where complete surgical excision was in doubt. We randomly assigned patients (1:2) to either upfront surgery and consideration for adjuvant therapy (standard of care group) or neoadjuvant plus adjuvant dabrafenib and trametinib (8 weeks of neoadjuvant oral dabrafenib 150 mg twice per day and oral trametinib 2 mg per day followed by surgery, then up to 44 weeks of adjuvant dabrafenib plus trametinib starting 1 week after surgery for a total of 52 weeks of treatment). Randomisation was not masked and was implemented by the clinical trial conduct website maintained by the trial centre. Patients were stratified by disease stage. The primary endpoint was investigator-assessed event-free survival (ie, patients who were alive without disease progression) at 12 months in the intent-to-treat population. This trial is registered at, number NCT02231775.

Between Oct 23, 2014, and April 13, 2016, we randomly assigned seven patients to standard of care, and 14 to neoadjuvant plus adjuvant dabrafenib and trametinib. The trial was stopped early after a prespecified interim safety analysis that occurred after a quarter of the participants had been accrued revealed significantly longer event-free survival with neoadjuvant plus adjuvant dabrafenib and trametinib than with standard of care. After a median follow-up of 18·6 months (IQR 14·6-23·1), significantly more patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive without disease progression than those receiving standard of care (ten [71%] of 14 patients vs none of seven in the standard of care group; median event-free survival was 19·7 months vs 2·9 months. Neoadjuvant plus adjuvant dabrafenib and trametinib were well tolerated with no occurrence of grade 4 adverse events or treatment-related deaths. The most common adverse events in the neoadjuvant plus adjuvant dabrafenib and trametinib group were expected grade 1-2 toxicities including chills (12 patients [92%]), headache (12 [92%]), and pyrexia (ten [77%]). The most common grade 3 adverse event was diarrhoea (two patients [15%]).

Neoadjuvant plus adjuvant dabrafenib and trametinib significantly improved event-free survival versus standard of care in patients with high-risk, surgically resectable, clinical stage III-IV melanoma. Although the trial finished early, limiting generalisability of the results, the findings provide proof-of-concept and support the rationale for further investigation of neoadjuvant approaches in this disease. This trial is currently continuing accrual as a single-arm study of neoadjuvant plus adjuvant dabrafenib and trametinib.

In this study of only 21 stage III/IV patients who had never taken BRAF/MEK, whose tumors were BRAF positive, and could be removed surgically, were divided in 2 groups. Folks with "metastases to bone, brain, or other sites where complete surgical excision was in doubt" were excluded.  7 got standard of care:  complete excision of their tumor and "consideration" of adjuvant therapy.  21 got the BRAF/MEK combo (dabrafenib and trametinib) BEFORE surgical removal of their lesion as well as AFTER!  Ten of the 14 treated with BRAF/MEK before and after excision were alive without disease progression "vs none of seven in the standard of care group"These results were deemed so good that this phase of the trial was stopped and only the neoadjuvant/adjuvant arm is continuing, and in fact, recruiting.

This is great news.  However, I do see several flies in this report.
1.  You researchers left out some folks in serious need of care...folks with brain, bone and other mets that you didn't see as a winning ticket.  I've been one of those peeps and was given adjuvant care.  Those folks need neo-adjuvant/adjuvant care as much (or more!!!!) than anybody!!  Here's a small tirade on their being left out of clinical trials:  A really good review of treatment data for Melanoma Brain Mets!!! (And this is from 2015!!!!!!!!)
2.  These are really small both arms.
3.  The fact that the 7 in the standard care arm were eligible for "consideration" of adjuvant care is pretty lame.  That language tells me that some chose to forego adjuvant care!!!  So OF COURSE!!! ~ those who had no additional care did less well!!!!  To provide greater clarity and benefit, the authors should have clearly defined the standard of care group in regard to whether they actually utilized BRAF/MEK after resection or not.
4.  Finally, I really don't care for the major drama, yet lack of real information, posed in this categorization of the 7 peeps in the standard of care group:  "more patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive without disease progression than those receiving standard of care (ten [71%] of 14 patients vs none of seven in the standard of care group".  At first blush it seems that all of the 7 are dead, along with the 4 out of the 14 in the neo/adjuvant group!!  Come on, Amaria!  You have better writing skills than this!  Some of these peeps may well have passed, but it is also possible that ALL these folks are alive, albeit with disease progression.  Clarification of that could easily have been included in this abstract and is hopefully made more clear in the actual published article.

Now...despite that critique...I am a huge fan of neoadjuvant treatment.  More and more, it is looking as though melanoma peeps treated in this way do better.  But, if nothing else, neoadjuvant treatment (treatment BEFORE surgical resection) provides decreased tumor bulk, therefore minimizing the invasiveness of the surgical resection.

You know me, Keep'n it💯!!!!!!!!!!  ~ les

Saturday, March 10, 2018

Sew Chaotically! - Pillow cases...again...for REALZ!!!

Some dear young peeps of mine are embarking on a lovely life together and found a sweet house, that reminds me a great deal of the one (both built in 1900!!) Brent and I started our crazy journey together in!!!  I thought it might be fun to offer up some pillow cases (or robes....though I would strongly recommend the pillow cases!!! HA!) as a house warming gift.  The idea was met with enthusiasm and I was sent a pic of bedding to match and a request for two standard sized pillow cases and two covers for 18 inch square throw pillows!!  Sew exciting!!!!

The bedding to match is to the left.  And this is what I picked.
I can't tell you why the burgundy looks different
depending on the photo...but it really
does match the little flower in the print to the left!

The finished products!!!
Replete with envelope style closures on each!
Life has its own ideas at times so through a misunderstanding, the pillow cases were sent to the WRONG address!!!  Yes, my poor shy intended peep went to the WRONG address to seek sent cases, left notes, but to no avail.  Gone they are!!  Perhaps they are making someone happy and slightly guilty all at the same time!!  At any rate, we begin again...

Back to the matching board!
Here's the fabric selection for this go round as the other was no longer available at my JoAnn's.  I think I might like it better!
2 standard sized cases.  2 to fit the throw pillows (fingers crossed)!!  All with their envelope finished ends!
There they be!  Practice makes perfect, no???
I have been informed that the last set arrived at the proper place and worked out well!!!  YAY!!!  Congrats you two!!  May you share many laughs, lovely moments, and brilliant bedding in your new home!!!  Much love, cess

Friday, March 9, 2018

CONCURRENT radiation and immunotherapy for brain mets is BEST!!!! (yes, AGAIN!!!)

"I know, I know!!!!"   I keep ranting about this.  And I will continue until it seeps into the pores of all melanoma (as well as NSCLC and renal cell carcinoma) patients and docs!!! Here are just a few zillions rants, posts, and data:  Yes, you SHOULD COMBINE radiation and immunotherapy!!!!
Now, there's this ~

Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. Chen, Douglass, Kleinberg, et al.  Int J Radiat Oncol Biol Phys. 2018 Mar 15. 

To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs).

We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs.

A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of greater than/= to 3 new BMs after SRS-SRT. Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone and compared with nonconcurrent SRS-SRT and ICI on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI or after ICI.  
Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.

Here folks looked at patients suffering from brain mets due to NSCLC, melanoma, and renal cell carcinoma.  Between 2010 and 2016, these peeps were treated with SRS-SRT and given either ipi, nivo or pembro.  CONCURRENT immunotherapy was defined as the meds having been given within 2 weeks of the radiation.  There were three groups:  1) those treated with radiation alone, 2) those treated with radiation and NON-concurrent immunotherapy, 3) and those treated with radiation and CONCURRENT immunotherapy.  260 patients were given radiation to 623 brain mets.  181 had radiation alone.  70 patients got radiation and immunotherapy with 35% of those attaining radiation concurrent with immunotherapy.  Overall survival for radiation alone = 12.9 months.  OS for radiation and NON-concurrent immunotherapy = 14.5 months.  OS for radiation with CONCURRENT immunotherapy = 24.7 months.  This was true no matter if the radiation was given before or after the immunotherapy....AND....wait for it....CONCURRENT administration of immunotherapy and radiation did NOT cause increased immune side effects NOR an increased rate of neurologic problems!!!!!!!!!!!!!!!!!!!  However, CONCURRENT immunotherapy and radiation DID decrease development of additional brain mets later!!!!

Come on folks!!!  This matters.  This is important.  This changes SAVES lives!!!  Do NOT settle for less.  If you have brain mets, demand CONCURRENT immunotherapy and SRS!!!!  There is more than enough proof.  It makes a positive difference!!! - c