Monday, March 27, 2017

Side effects of immunotherapy - Part 8

In the ongoing saga...see the previous post:  Side effects of immunotherapy - Part 7

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Behling, Kaes, Munzel, et al. Melanoma Res. 2017 Apr;27.

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.
Two cases of clinical myasthenia gravis associated with pembrolizumab use in responding melanoma patients. Nguyen, Kuo, Budiman, Christie. Melanoma Res. 2017 April.

Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients. One case is in an 81-year-old man and the second case in an 86-year-old woman, both with BRAF-negative metastatic melanoma receiving pembrolizumab. These two cases of ocular only associated myasthenic syndrome appeared 7 and 11 weeks after the initiation of pembrolizumab. We conclude that the condition is most likely associated with pembrolizumab as symptoms started after treatment with pembrolizumab, neither patient had other evidence of neurological cause for presentation, and symptoms also improved rapidly with administration of steroids. Both patients showed good oncological response to anti-PD1 treatment and one patient successfully continued to receive ongoing treatment with no further complications.

PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis. Wu, Hong, Zhang, et al. Lancet Oncol. 2017 Mar 3.
Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% for all-grade and 1.53% for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types.

Autoimmune limbic encephalitis with anti-contactin-associated protein-like 2 antibody secondary to pembrolizumab therapy. Brown, Hissaria, Hsieh, et al. J Neuroimmunol. 2017 Apr 15.

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma.

Be safe.  Be aware.  Seek help if you think you need it!  Hang tough, ratties!  Hang tough!  - c

Sunday, March 26, 2017

What tangled 'paths' we weave: Nilotinib for KIT mutated melanoma and Buparlisib for the PI3K pathway in melanoma brain mets

Melanoma mutations can be confusing to say the least.  This diagram helps a bit:

Here's credit and an explanation:  Melanoma Pathways....A Melanoma Molecular Disease Model

NRAS and KIT mutated patients have not had the luxury of good responses to immunotherapy and targeted therapies currently being utilized in melanoma.  But, now there's this:

Efficacy and Safety of Nilotinib in Patients With KIT-Mutated Metastatic or Inoperable Melanoma: Final Results From the Global, Single-Arm, Phase II TEAM Trial. Guo, Carcjal, Drummer,..., Hodi. Ann Oncol. 2017 Mar 6. 

The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT -mutated advanced melanoma without prior KIT inhibitor treatment.

Forty-two patients with KIT -mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT -mutated melanomas. Thirteen patients were randomized to DTIC prior to the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors.

ORR was 26.2%, sufficient to reject the null hypothesis (ORR less than or = to 10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease, 10 (23.8%) had progressive disease, and 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, 4 with an L576P mutation. The median progression-free survival and overall survival were 4.2 months and 18.0 months, respectively. Three of 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib.

Nilotinib activity in patients with advanced KIT -mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.  

42 patients is not a ton.  26.2% ORR...with all of those being partial responses is not fabulous...but it is definitely SOMETHING!!!  Hey, I was over the moon when ipi was approved with its 15% response rate!!!  

And ~ if you refer to the chart above will see the PI3K pathway....

Here is an initial post re the PI3K pathway in relation to brain mets by Dr. Davies:  PI3K/AKT - a pathway with potential for treating melanoma brain mets

And now there's this mousie medicine....

PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo. Niessner, Schmitz, Tabatabai, et al. Clin Cancer Res. 2016 Dec 1.

Great advances have recently been made in treating patients with metastatic melanoma. However, existing therapies are less effective on cerebral than extracerebral metastases. This highlights the potential role of the brain environment on tumor progression and drug resistance and underlines the need for "brain-specific" therapies. We previously showed that the PI3K-AKT survival pathway is hyperactivated in brain but not extracerebral melanoma metastases and that astrocyte-conditioned medium activates AKT in melanoma cells in vitro We therefore tested the PI3K inhibitor buparlisib as an antitumor agent for melanoma brain metastases.

Buparlisib inhibited AKT activity, decreased proliferation, and induced apoptosis in metastatic melanoma cell lines and short-term brain melanoma cells, irrespective of their BRAF and NRAS mutation status. In addition, buparlisib inhibited hyperactivated AKT and induced apoptosis in melanoma cells that were stimulated with astrocyte-conditioned medium. The growth of tumors induced by injecting human BRAF- and NRAS-mutant metastatic melanoma cells into the brain of mice was significantly inhibited by buparlisib.
These results emphasize the value of targeting the PI3K pathway as a strategy to develop drugs for melanoma brain metastases.

This last is certainly in its baby steps...  But, hey!  On these paths, any steps at all are a needed start!!
(However, there are many PI3K inhibitors in studies for other cancers - Buparlisib [drug noted above] and Alpelisib [for breast cancer], Duvelisib [hematologic malignancies], TGR1202 [follicular lymphoma].)

Thanks, mousies.  Hang tough, ratties!  - c

Saturday, March 25, 2017

Circulating DNA predicts response to anti-PD1

One more thing I have been yelling about for years!!!  Medicine now has the technology to determine all sorts of things via a simple blood draw. Circulating tiny bits of tumor DNA floating through our blood can tell docs what type of tumor we have, predict response to a given treatment and let us know how the treatment is working.  Here is a link to years of posts:  Circulating DNA in melanoma treatment from 2014 til now!!

Now there's this:

Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Lee, Long, Boyd, et al. Ann Oncol. 2017 Jan 24. 

Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information.

We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab.

ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance. RECIST response was 72% (26/36) in Group A (undetectable ctDNA at baseline), 77% (17/22) in Group B (elevated ctDNA at baseline but undetectable within 12 weeks of therapy) and 6% (1/18) in Group C (elevated ctDNA at baseline and remained elevated during treatment). The median PFS was not reached in groups A and B and was 2.7 months for Group C. The median OS was not reached for Groups A and B and was 9.2 months for Group C . The poor outcome measures associated with Group C remained significant in multivariate analysis adjusted for LDH, performance status, tumour stage and disease volume. The predictive value for ctDNA for response was confirmed in a separate validation cohort.

Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS. Patients who had a persistently elevated ctDNA on therapy had a poor prognosis, and this may guide combination and sequencing of subsequent therapies.

Clearly, per the results of this study, patients did best when their circulating tumor DNA became undetectable under treatment.  Conversely, as one might suspect, when ctDNA remained elevated despite treatment, folks did less well...even when researchers controlled for known prognostic indicators like LDH, disease volume, etc.

We KNOW these facts.  We HAVE the technical ability.  WHY is this not standard of care??

Hang in there, ratties.  love, c

Friday, March 24, 2017

Chaotic Cookery! - From Someone Else's Table: Turkey Legs Confit

Duck legs confit in Sarlat, France. Roast lamb that was basically a confit in Spain (pic below). Turkey leg confit in Chicago at the Purple Pig.  Now......Turkey Legs home in TN!!!

For my attempt I basically adapted a Bon Appetit recipe for Chicken Leg Confit.

Turkey Leg Confit:  Salt and pepper two turkey legs.  Place in a baking dish in which the legs fit with as little extra space as possible. Cut 1 bulb of garlic in half.  Quarter 2 shallots.  Leave paper on all and tuck them in between and around the legs.  Toss in thyme sprigs.  Come close to covering the legs with olive oil.  Cover and place in oven at 275 for 3 hours.  Then, uncover and cook for 30 more minutes.  This can be done as much as 2 days before serving.  And....don't fret about all the oil.  You will not have oily legs and the flavored oil can be used in more roasted bird, with roasted potatoes or other veggies.

Prepped and ready for the oven.

First step done!

Ready to eat!!!
Once your are ready to serve.  Remove the legs from their oil bath.  Place on oven safe tray or pan and roast at 425 for about 15 - 20 minutes until browned and skin crisp.
So yummy and easy!  What an elevation for lowly legs.  And....about those sides....

B's Spicy Roasted Potatoes with Cool Yogurt Dipping Sauce - from Williams-Sonoma's New Flavors for Vegetables

Cut about 3 pounds of peeled russet potatoes (any kind really) into bite sized pieces and toss with 2 T Harissa (B decreases the amount for my whimpy self), 1/4 t cayenne, 1 T sesame seeds, and 1 t salt.  Meanwhile, heat a roasting pan with about 1/4 c oil (in this case we used the oil the turkey legs were cooked in!!) drizzled in the bottom.  Once it is hot, carefully add the potatoes and toss them to coat in the oil.  Arrange the potatoes in a single layer.  Roast until the potato pieces are nicely browned, 25-30 minutes.  Flip over and roast until tender and browned and crisp outside, about 15 minutes longer.

While roasting - mix up a yogurt sauce with 1 cup Greek yogurt, 1/2 bunch fresh copped mint (or parsley or dried herbs), and juice from 1/2 lemon.  Season with salt and pepper.

For this dinner, I also sauteed some chard with the roasted scallions and some of the garlic and oil from the turkey legs.

So yummy....Try it!  Turkey legs influenced by tables in Spain and France....not to mention Chicago!!!  You can never go wrong eating and cooking - From Someone Else's Table! - c

Wednesday, March 22, 2017

Think Obama Care vs Trump Care is just partisan bickering? NOPE! It is all about LIFE and HEALTH for you and those you love!

I know, I know!!!!  There is absolutely no greater mood killing, depressing and dismaying topic to discuss than insurance or politics!  And, in this context...we have both!!!  In the words of the Tweeter-in-chief, "SAD!!!!" Still, Obama Care vs Trump Care is too important to ignore! we go....

This is an amazing video that breaks it DOWN!!!

Ezra Klein: The perverse reality of the Republican health care bill

This is a particularly telling interview from NPR of an ex-insurance exec ~ and you know how much I love those vultures!!!

Insurance Industry Worried By GOP Plan To Replace Obamacare, Consultant Says

And who always suffers the most when folks who think the "bottom line" matters more than people, call the shots?  The poorest, sickest, oldest, youngest - our most vulnerable:

From The Atlantic: The Silent Victims of the GOP Health-Care Proposal “Children are the largest single group of beneficiaries on Medicaid—and they don't vote.”

If you think "Obama Care" didn't help you and yours because you have private insurance, you have a lot to rethink!!!

The ACA forced insurance companies to abandon lifetime caps!  Grand totals paid out by insurance plans, no matter that a family has paid into them for years, but ended all future payments for your dad, because after he had ONE significant surgery he maxed out his policy (never mind that he had never used it before)!  Or, your baby was no longer covered by your family plan because she stayed a few nights in the NICU right after birth. Before the ACA, that was it! No more payments.  No more coverage, you were done - UNTIL the ACA changed that horrific policy and made insurance companies play fair!

The ACA forced insurance companies to stop discrimination against those of us with pre-existing conditions.  And if you think melanoma and cancer were the only "pre-existing" diagnoses that allowed insurance companies to charge you more or not sell you insurance at any price...well, that's not true.  Children with a history of a broken leg at age 4, which healed perfectly, found themselves uncovered at all or just not "that leg" should, heaven forbid it suffer an injury in an accident, football game, or develop a sarcoma.  And folks with high blood pressure, diabetes, or  a heart attack...well, they could just forget it.

The ACA stopped insurance companies from taking Americans' hard earned money for junk plans that didn't pay anything when they needed well check ups for their kids, vaccines, pap smears, mamograms, basic care when sick with a cold, flu, pneumonia, asthma...I could go on.  Those plans were a big surprise when folks tried to use them to attain basic healthcare. They were deemed illegal by the ACA.

The ACA expanded medicaid in the states willing to accept the help to cover our working poor and children.

The ACA did NOT cause your insurance rates to go up!!  Insurance company execs did that...with the approval of state legislatures. Executives who make 15-20 million dollars a year for their amazing management skills.  THEY decided they needed even our expense!!!

The ACA allowed children up to the age of 26 to stay on their family's plans.

The ACA is not perfect.  There are many ways in which it could be improved.  So why don't we??? Cause here's the deal...


The health of our nation, physical and mental, is the vital living human infrastructure of our society. That infrastructure is absolutely essential for everything else. It includes everyone from the infant to the elder. It encompasses all parts of life: birth, childhood, adulthood, old age and death. It is what and how we eat and drink. It is the air we breathe. Procreation, pain, suffering, joy and fulfillment are all rooted in our health. The health of our nation is sacred and shared. The health of one literally affects the health of all. Wisely, health is enshrined in our Declaration of Independence: Life, Liberty and the Pursuit of Happiness. It is life, that comes first as a necessary condition and the right to health care is the concrete embodiment of that right to life. There are those who are blind to the communal nature of health. They deny health care as a right, seeing it only as a privilege for the few with resources. A privilege restricted to those whom they consider innocent, powerful or wealthy enough to save from disease, suffering and death. We must fight for the right to our health care and our lives. All of us are innocent enough, powerful enough, rich and deserving enough to have the same opportunities for healthcare. So, we join the struggle for our health with the United States Congress. It is the struggle for and of our lives and those we love. It is also the struggle for the survival and spirit of the United States. We will not lose because we cannot lose.   (Just a little op-ed written by me and B)

Indeed, the health of our neighbors, friends and family - our fellow AMERICANS - is our most essential infrastructure.  The health of our nation is the well from which all else springs.

I believe in all Americans.  I believe that healthcare is a right ~ one that belongs to all of us ~ those is the prime of health with lots of money, as well as those who are less fortunate and perhaps more in need.  No matter where you fall on that scale is a fluid place.  One minute you are gainfully employed with bountiful health, the next you are facing a life threatening illness, too ill to work (NOT too lazy!!!).  But, thanks to science and the generous spirit of your fellow can cross the bridge to health and productivity once more.  YES, WE CAN do that for each other!  And....we should. 

Much love, les

Monday, March 20, 2017

Surprise, surprise, surprise! The sooner brain mets are found - the better folks with melanoma, breast cancer,!!!

Do you ever read a statistical study that involves bunches of patients, expert researchers, thousands of samples, statisticians and probably a significant chunk of change and think, "No shit, Sherlock!!!"? It happens to me all the time! ~ Just out!  New expert findings regarding obesity in children!  In this new research, utilizing multiple offices and institutions, patient and parental questionnaires, cox 2 data analysis, and all sorts of other jabber, jabber - We have found that obese children are more sedentary and consume more calories than their thinner peers!!!"

In that vein...there is this...

Toward the complete control of brain metastases using surveillance screening and stereotactic radiosurgery. Wolf, Kvint, Chachoua, Pavlick, et al. J Neurosurg. 2017 Feb 17.

The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease. Stereotactic radiosurgery (SRS) is a first-line management option for brain metastases. The purpose of this study was to determine if there is a threshold tumor size below which local control (LC) rates approach 100%, and to relate these findings to the use of routine surveillance brain imaging.
From a prospective registry, 200 patients with 1237 brain metastases were identified who underwent SRS between December 2012 and May 2015. The median imaging follow-up duration was 7.9 months, and the median margin dose was 18 Gy. The maximal diameter and volume of tumors were measured. Histological analysis included 96 patients with non-small cell lung cancers (NSCLCs), 40 with melanoma, 35 with breast cancer, and 29 with other histologies.
Almost 50% of brain metastases were NSCLCs and commonly measured less than 6 mm in maximal diameter or 70 mm3 in volume. Thirty-three of 1237 tumors had local progression at a median of 8.8 months. The 1- and 2-year actuarial LC rates were 97% and 93%, respectively. LC of 100% was achieved for all intracranial metastases less than 100 mm3 in volume or 6 mm in diameter. Patients whose tumors at first SRS were less than 10 mm maximal diameter or a volume of 250 mm3 had improved overall survival.  
SRS can achieve LC rates approaching 100% for subcentimeter metastases. The earlier initial detection and prompt treatment of small intracranial metastases may prevent the development of neurological symptoms and the need for resection, and improve overall survival. To identify tumors when they are small, routine surveillance brain imaging should be considered as part of the standard of care for lung, breast, and melanoma metastases.
#1.  Well, duh.  If you find brain tumors when they are small and zap them out of existence, patients do not suffer as much damage and live longer.
#2.  I don't I agree with the opening salvo:  "The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease."  At least in the sense that, as melanoma patients live longer, DUE to systemic therapies....we are seeing more of everything...cause these peeps are not dead!  Also, I fear that since we have learned that we can zap many, many brain tumors sequentially or simultaneously with SRS and melanoma patients actually respond positively as they did NOT when only whole brain radiation was offered or utilized, I fear that some docs are not being as aggressive as they should be in finding a systemic therapy that actually DOES work for the patient who is having brain met after brain met!!!
(Here's a recent post that supports my disbelief!!! - SRS with any systemic therapy helps response in melanoma brain mets...)
#3.  Instead of using this data as a published study to pad your researcher dear researchers!!!....use it to get insurance companies in line with paying for melanoma patients' brain imaging...instead of telling ANY melanoma patient, much less one status post BRAIN TUMORS - 
"You may experience the pleasure of your CT scans as planned, however in regard to the MRI...."Based on eviCore Oncology Imaging Guidelines, we are unable to approve the study your doctor requested.  Your records show that you have SKIN DISEASE that is stage 2B to stage 4.  Follow up magnetic resonance imaging, detailed picture study, of your brain is supported for this problem once per year for the first 5 years after your skin disease was found.  Your records do not show that this applies to you. This decision just means your health plan won't pay for the service.  You can still receive the service, but you will need to pay for it yourself.  {signed} Michele Awobuluyi, MD"   (This was the Blue Cross response to my onc's request for my now annual can check out the entire outrageous story here:  August 2016: And then there's me...)
Researchers, you have the data, the reputation, the expertise, and the clout to put the pressure on insurance companies to provide the care that your patients need.  Do it!!!!
#4.  And since this is one more perfect opportunity to say it, "Michele Awobuluyi, MD, NYU alum - you are an ass and an idiot, a disgrace to your profession and a danger to society."  I hope you google your own name!!!
Being a rattie is tiring!  Hang tough, ratties.  Hang tough. - c

Sunday, March 19, 2017

PV-10 followed by radiation = ORR of 86% in in-transit, dermal and sub q melanoma

I have been yelling about intralesionals and Rose Bengal (PV-10) for YEARS!!!!!!!!!!!!!

Here's a review:
2016: Intralesional Therapy....and patterns of response from the T-VEC OPTiM trial
2016: Intralesional PV-10 (Rose Bengal, y'all!!!) positive treatment for in-transit melanoma
ASCO 2016: New studies! Rose Bengal and Pembro for Stage IV y'all!!! Enrolling! For Stage IIIb/c: PV-10 vs T-VEC.
2016: Study on Intralesional Rose Bengal out of Moffitt...we know a bit more about HOW it works!!!
2016: CAVATAK - intralesional therapy derived from the coxsackievirus
And finally, this one...with 3 links to additional reports from 2014, 2013, and 2012, and2014: More info from ASCO....PV-10...Rose Bengal for melanoma....

Now, there is this......

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.

In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction.
An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy.
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.  
The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects.

Small numbers of patients, but the results - "Not bad, not at all bad!!!" - c