Prospective Phase II US study: complete clinical responders

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Ajane
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Prospective Phase II US study: complete clinical responders

Postby Ajane » Sun Feb 01, 2015 6:58 am

FYI. A prospective phase II study has recently begun enrolling patients at 20 institutions across the United States, and non-surgical management will be offered to patients whose tumors fully disappear after initial chemotherapy and radiation.

American Society of Clinical Oncology, just released January 15, 2015.

“Avoiding surgery has the potential to significantly improve quality of life for patients, for example by avoiding a colostomy. Longer follow-up is needed, however, to be sure that this approach does not result in higher cancer recurrences. A prospective study in the United States evaluating this important issue is now enrolling patients,” said Smitha S. Krishnamurthi, MD, moderator of today’s presscast and ASCO expert.

ALEXANDRIA, Va. – A retrospective review of clinical data on 145 patients with stage I-III rectal cancer indicates that patients whose tumors completely disappeared after treatment with chemoradiation and systemic chemotherapy (known as a complete response) had similar four-year survival rates regardless of whether they had immediate surgery or pursued a “watch and wait” surveillance approach. The findings add to growing evidence suggesting that, with frequent follow-up exams after initial chemotherapy and radiation, select patients with rectal cancer can achieve excellent outcomes while avoiding the risks and complications of rectal surgery. The study will be presented at the upcoming 2015 Gastrointestinal Cancers Symposiumin San Francisco.

“We believe that our results will encourage more doctors to consider this watch and wait approach in patients with clinical complete response as an alternative to immediate rectal surgery, at least for some patients,” said senior study author Philip Paty, MD, a surgical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, NY. “From my experience, most patients are willing to accept some risk to defer rectal surgery in hope of avoiding major surgery and preserving rectal function.”

Dr. Paty stated that in about 40 to 50 percent of patients with stage I rectal cancer and 30 to 40 percent of patients with stage II-III cancer, tumors disappear clinically after initial treatment with chemoradiation and systemic chemotherapy. He suggests that those patients are potential candidates for the watch and wait approach. By avoiding rectal surgery, patients are spared of its risks, including impaired bowel and sexual function, which can substantially diminish quality of life.

In the present report, researchers retrospectively analyzed data that were collected at Memorial Sloan-Kettering Cancer Center between 2006 and 2014. Patients with stage I-III rectal cancer who received radiation and chemotherapy (neoadjuvant therapy) and who experienced complete tumor regression were either followed by watchful waiting (non-surgical management) or taken for rectal surgery. Patients undergoing the watchful waiting approach were initially followed at three- to four-month intervals by digital rectal and endoscopic exams and at six-month intervals by cross-sectional imaging. Median follow-up in this report is 3.3 years.

Rectal surgery was deferred in 73 patients who achieved a clinical complete response after chemotherapy and radiation (no cancer detected on physical exam, endoscopy, or imaging). Among those 73 patients, 74 percent experienced durable tumor regression and avoided rectal surgery; 26 percent eventually underwent rectal surgery to treat tumor regrowth.

In a non-randomized comparison, researchers found that the outcomes achieved in this group of patients were similar to the outcomes of 72 patients who underwent standard rectal surgery and experienced a pathologic complete response (no viable cancer cells found on microscopic exam of surgically removed tissue): the four-year overall survival rate was 91 percent in the no-surgery group vs. 95 percent in the standard surgery group. No significant differences were noted in the number of distant recurrences between the two groups.

According to the authors, this is one of the largest experiences of its kind, building on prior evidence from research conducted in Brazil and the Netherlands. Non-surgical management of rectal cancer is becoming increasingly accepted as a standard option worldwide. A prospective phase II study has recently begun enrolling patients at 20 institutions across the United States, and non-surgical management will be offered to patients whose tumors fully disappear after initial chemotherapy and radiation.
7/13, T2, G3, Ultra-low. CEA 5.7 KRAS Wild, MSS
8-9/13 6 wks Xeloda/radiation
12/13 TEM pCR NED
5/15 CEA 4.6 PET 1.5 cm met, UL Lobectomy
6-10/15: Rounds 1-2 Xelox+Avastin; 3-8 Folfox+Avastin
10/15-4/16: 12 rounds Avastin
9/2016 CEA 4.2, 12 mm AP node
11/2016 CEA 4.3. PET/CT. 16mm AP nodal met removed
4 wks chemorad
2/2017 NED CEA 2.4
Carafate to tx esophageal ulcers caused by rad
Avastin maintenance postponed

2 Corinthians 12:9

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CRguy
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Re: Prospective Phase II US study: complete clinical respond

Postby CRguy » Sun Feb 01, 2015 2:26 pm

I also believe Dr. Axel Grothey championed this perspective initially ?????

Knowing what I know NOW ( I had pCR = pathological complete response to neoadjuvant chemoradiation
I would have skipped the surgery as per this study which is dealing with only clinical CR metrics.

BUTT back then .. who knew ?????

I hope this gives a few folks an alternate route of treatments for applicable situations.

Harmony all
CRguy
Caregiver x 4
Stage IV A rectal cancer/lung met
13 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

Ktwirls
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Re: Prospective Phase II US study: complete clinical respond

Postby Ktwirls » Sun Feb 01, 2015 8:32 pm

I am so glad to hear about this in the US. I had heard about the UK study that was going on back in 2010 (when I was first dx). I chose to forgo the apr with posterior pelvic exenteration after having a complete clinical response from folfox and chemo/radiation. Mine did come back in 2014 ( a little higher up than original spot) and then had the same surgery that I was supposed to have the first time around. No spread anywhere else and surgery produced clear margins and no lymph nodes were positive (which the first time around from scans and MRI they had said several nodes positive). Knock on wood, say a pray I am now NED. I remember how crazy (by drs and other CRC patients it) was considered to even think about not doing it. I even lost my oncologist over it and transferred care. Even though it came back (I was not under any allusion that it couldn't come back) I was so glad to have that time without that surgery and all the horribleness that comes from it. I often hope to run into the surgeon who said I would be dead in a year if I didn't have the surgery. I wonder what he would think of these trials. I am glad they are open to exploring another option for some people.
Kim Ann, mom to 6
dx May 2010 age 37 (symptoms started in pregnancy age 36)
Rectal Cancer stage 3b T4,N1
FolFox 8, chem/rad 6wks
It came back March 2014
APR w/ PPE surgery, now on chemo, latest scan NED
http://cancercaughtme.blogspot.com/

Ajane
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Re: Prospective Phase II US study: complete clinical respond

Postby Ajane » Sun Feb 01, 2015 9:52 pm

CR, you were right to assume that I primarily posted this for the benefit of the newbies who might be candidates. They need to know it's an option now! As you stated, it will allow the ones who achieve a complete clinical response an alternate route.

Yes, times are changing. I'm sorry that the timing of this wasn't in your favor. "This is how complete clinical responders will likely be treated from here on out," words loosely taken from my surgeon just last week. In our little corner of the world, I was his first "watch and wait" case. Because of that but also because I was a grade 3, T2, he took it a step further and did the TEM to determine pCR, which gave us both a bit more peace of mind. I know I've great odds of being in the clear long term, but as we all know, that doesn't mean there's not some unseen thing potentially brewing. I just try to enjoy each day I'm given.

KT, glad you had that time too and more importantly you're NED now! Our plan too is to do the surgery we would have done initially anyway (an APR) if I have a local recurrence. I'm 18 months post-chemorad and almost 14 months post-TEM. Still got a ways to go, but so far so good.
7/13, T2, G3, Ultra-low. CEA 5.7 KRAS Wild, MSS
8-9/13 6 wks Xeloda/radiation
12/13 TEM pCR NED
5/15 CEA 4.6 PET 1.5 cm met, UL Lobectomy
6-10/15: Rounds 1-2 Xelox+Avastin; 3-8 Folfox+Avastin
10/15-4/16: 12 rounds Avastin
9/2016 CEA 4.2, 12 mm AP node
11/2016 CEA 4.3. PET/CT. 16mm AP nodal met removed
4 wks chemorad
2/2017 NED CEA 2.4
Carafate to tx esophageal ulcers caused by rad
Avastin maintenance postponed

2 Corinthians 12:9

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muskokamike
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Re: Prospective Phase II US study: complete clinical respond

Postby muskokamike » Sun Feb 01, 2015 10:47 pm

Hmmmm. I personally am glad I had the surgery. I am almost a year out from the major surgery after my chemo/rad and looking back it was tough. I have no complications from the original surgery and my only real side effect was from the mop up chemo I elected to do that being neuropathy. When I was dx I was really not given the option of no surgery. My surgeon was just hoping to shrink the tumor so it would be easier to remove and prevent a permanent colostomy. My pathology came back as a complete response and even though I lost a foot of colon and rectum I knew that for sure the cancer was out of my body. Sure there could still be microscopic cells in my system and that is why I elected to do the evil Folfox. If cancer does want a rematch then in my heart I know I did everything the first time I could possibly do to avoid recurrence. It is a very personal decision one has to make but I was in great shape going in and that worked in my favour. I just like the peace of mind of a complete pathological response over a complete clinical response but everyone is different.
53M Dx rc10/31/13
WTF!
CT scan, BONE scan
MRI/T3N0M0 1 suspicious node
5 wks chemo/rad
LAR open TME 2/26/14
temp ileo
0/24 nodes pCR/pathological
Mop up Folfox (8) Mar/28-Jul/4
Aug/14 clear CT scan
8/27/14 reversal
Feb/15 clear scope
July/15 clear CT scan
Feb/16 clear CT scan
Feb/17 clear CT scan
Feb/18 clear scope
Feb/18 clear CT scan
Sep/19 clear CT scan DISCHARGED!
CEA levels 1.6 dx
1.6,1.4,1.7,2.4,2.9, 2.7 2.3 2.5 2.2 2.1 2.5 2.6 2.7
2.7 Sept 19
0-4 normal
https://kicknasscancersass.blogspot.com/

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CRguy
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Re: Prospective Phase II US study: complete clinical respond

Postby CRguy » Sun Feb 01, 2015 11:54 pm

Ajane wrote:he took it a step further and did the TEM to determine pCR,

and this you see is EXACTLY where the rubber hits the road ..... clinical CR versus pathological CR
because I had pCR + surgery + adjuvant chemo ... AND still had a lung met we resected 3 years later.

My big :?: here is : " where would I have been in this NEW scenario without the resection and adjuvant after initial Dx ?????
..... IF I still had a met and had to have more surgery/chemo 3 years later ?????"

I am always a big fan of vigilant follow up, but am a bit concerned when the tide turns to " OK cCR... SO ... don't need this don't need that ... ????? "

I still would have passed on Sx BUTT I am very aggressive and obnoxious in pushing the Docs as my own advocate ...
what about folks who are not ?

Still on the learning curve it seems.

Cheers all
CR
Caregiver x 4
Stage IV A rectal cancer/lung met
13 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

Ajane
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Re: Prospective Phase II US study: complete clinical respond

Postby Ajane » Mon Feb 02, 2015 1:13 am

Mike and CR, don't get me wrong, I'm not proposing it's the road best chosen for all who are candidates. I do however strongly believe it is another option that should be open for discussion for those who achieve cCR. Having said that, it's a personal decision and certainly not an easy path. Symptoms led me to believe just last fall that I had a recurrence. Fortunately that was not the case. Yes, strict adherence to follow up care is critical.

Edit: CR, keep in mind that I was also a late stage one. You might have been as well. I don't know. But I'm also 60 years old with other health issues that played a part in my decision that could have negatively impacted the surgery, recovery, and longterm care of the permanent colostomy/Barbie butt. Yes, I know there are no guarantees with pCR, but I take comfort in knowing there was " No significant differences were noted in the number of distant recurrences between the two groups." One could say I'm wearing blinders. Maybe I am, but it's the path I've chosen to run my race.
Last edited by Ajane on Mon Feb 02, 2015 9:35 am, edited 3 times in total.
7/13, T2, G3, Ultra-low. CEA 5.7 KRAS Wild, MSS
8-9/13 6 wks Xeloda/radiation
12/13 TEM pCR NED
5/15 CEA 4.6 PET 1.5 cm met, UL Lobectomy
6-10/15: Rounds 1-2 Xelox+Avastin; 3-8 Folfox+Avastin
10/15-4/16: 12 rounds Avastin
9/2016 CEA 4.2, 12 mm AP node
11/2016 CEA 4.3. PET/CT. 16mm AP nodal met removed
4 wks chemorad
2/2017 NED CEA 2.4
Carafate to tx esophageal ulcers caused by rad
Avastin maintenance postponed

2 Corinthians 12:9

weisssoccermom
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Location: Pacific NW

Re: Prospective Phase II US study: complete clinical respond

Postby weisssoccermom » Mon Feb 02, 2015 1:22 am

When I was diagnosed, I actually contacted a Dr. David Medwell in Pittsburgh and Dr. Habr-Gama (Brazil) who have done studies on this (the Brazil study which was referenced in the article is most likely that of Dr. Habr-Gama) and went along with this line of thinking with a slight twist. There was no way that I wanted the LAR and had to fight long and hard to find a surgeon who would agree with me. It is difficult with rectal cancer to really know whether someone has had a complete response to the chemoradiation. It can appear that there is a complete clinical response but one doesn't know if there are still cancer cells lurking in the rectal wall. I didn't want everything out in order to find out, so instead opted for the excision, as a 'biopsy of sorts. By all accounts, I had a complete clinical response but wanted to truly know if there was a complete pathological response in the rectal wall. The full thickness excision offered me that information.

I also hope that surgeons will be able to tweak treatments to get the best response and yet minimize the effects of rectal cancer surgery. The old figures of relapse after excision didn't take into consideration the treatments of chemo and radiation. I'm not sure I would feel entirely comfortable not having an excision....if for no other reason than to find out what, if any cells were remaining in the rectal wall. I do, however, totally agree with super meticulous follow up exams.....probably more frequently than if a patient had the LAR/APR. For me, that trade off was worth it.....didn't really like so many exams all the time but glad I didn't have to deal with any of the issues that are so often associated with the other surgeries. Glad to see that there are docs out there willing to 'think outside the box'. Mike...just an FYI....the studies have shown (and trust me, I researched this) that with a three prong approach: chemoradiation, excision for biopsy purposes, follow up chemo, the rates of recurrence are within one percentage of those with the more radical surgery. I'm not saying it is for everyone and certainly docs aren't all on board yet either (just like they weren't when the LAR option came into the picture) but it is an option which should be given to the patient if he/she wants to pursue it.
Dx 6/22/2006 IIA rectal cancer
6 wks rad/Xeloda -finished 9/06
1st attempt transanal excision 11/06
11/17/06 XELOX 1 cycle
5 months Xeloda only Dec '06 - April '07
10+ blood clots, 1 DVT 1/07
transanal excision 4/20/07 path-NO CANCER CELLS!
NED now and forever!
Perform random acts of kindness

Ajane
Posts: 427
Joined: Tue Jul 23, 2013 3:03 am

Re: Prospective Phase II US study: complete clinical respond

Postby Ajane » Mon Feb 02, 2015 2:05 am

Jaynee, thanks for chiming in. I think you just hit the nail on the head. If surgeons would agree to or if patients would advocate for TE or TEM after they're surgeon sees what he thinks is a cCR, then they would have the answer they need. They'd know for certain they've achieved pCR. Fortunately, my surgeon and I were on the same page!
7/13, T2, G3, Ultra-low. CEA 5.7 KRAS Wild, MSS
8-9/13 6 wks Xeloda/radiation
12/13 TEM pCR NED
5/15 CEA 4.6 PET 1.5 cm met, UL Lobectomy
6-10/15: Rounds 1-2 Xelox+Avastin; 3-8 Folfox+Avastin
10/15-4/16: 12 rounds Avastin
9/2016 CEA 4.2, 12 mm AP node
11/2016 CEA 4.3. PET/CT. 16mm AP nodal met removed
4 wks chemorad
2/2017 NED CEA 2.4
Carafate to tx esophageal ulcers caused by rad
Avastin maintenance postponed

2 Corinthians 12:9

ticktock10
Posts: 49
Joined: Fri Mar 07, 2014 3:49 am

Re: Prospective Phase II US study: complete clinical respond

Postby ticktock10 » Mon Feb 02, 2015 4:05 am

Thanks for posting this. It adds a bit more evidence to the argument that 'watch and wait' is now a valid option for people who experience a complete clinical response after chemo-rad.

The 26% local recurrence rate is interesting. It ties in broadly with my own research but it is very difficult to generalise when the total numbers involved in these studies are quite low. I did a lot of reading before making my decision and I tried to find out the recurrence rate in each of the studies which had been done. It varied a lot, one study from Holland was 5-10% (only 1 or 2 out of 21) another from the UK was closer to 40% but they tended to come in between 15-30%.

I did a deal with my surgeon that if there is any local recurrence we go straight to APR, so if that is the worst that happens then I will be OK with it and I will appreciate the extra time I had without the bag, similar to Kim Ann. Obviously, there is the possibility of distant spread and that is the big fear, but reports like this one help me remember that the choice I made was rational.

I have a follow-up MRI scan next week and I am feeling a little bit of scanxiety, so thanks again for posting!
Oct 2013 - Dx Stage 2/3 low rectal cancer
Dec 2013- 6 weeks neo-adjuvant chemo-rad
Apr 2014 - PET and MRI show 'complete response'
May 2014 - Chose 'watch and wait' instead of APR surgery
Jun-Sep 2014 - 'adjuvant' chemo - 5FU
Sep 2014 - PET and MRI clear

Ajane
Posts: 427
Joined: Tue Jul 23, 2013 3:03 am

Re: Prospective Phase II US study: complete clinical respond

Postby Ajane » Mon Feb 02, 2015 8:15 am

Ticktock, good luck to you! As they say here, I'll be swinging chickens and praying for you. Please let us know how it goes.
7/13, T2, G3, Ultra-low. CEA 5.7 KRAS Wild, MSS
8-9/13 6 wks Xeloda/radiation
12/13 TEM pCR NED
5/15 CEA 4.6 PET 1.5 cm met, UL Lobectomy
6-10/15: Rounds 1-2 Xelox+Avastin; 3-8 Folfox+Avastin
10/15-4/16: 12 rounds Avastin
9/2016 CEA 4.2, 12 mm AP node
11/2016 CEA 4.3. PET/CT. 16mm AP nodal met removed
4 wks chemorad
2/2017 NED CEA 2.4
Carafate to tx esophageal ulcers caused by rad
Avastin maintenance postponed

2 Corinthians 12:9

Coyote
Posts: 9
Joined: Mon Feb 02, 2015 2:55 pm

Re: Prospective Phase II US study: complete clinical respond

Postby Coyote » Mon Feb 02, 2015 4:14 pm

Hello. I am new to the group but have already learned a lot from your posts. Thanks for the generous sharing of info, opinions and experiences.
I am debating on whether to apply for this trial or to just try to find a Dr. who will prescribe a course chemo/radiation while allowing me to continue to work with my naturopath.
The drugs in the study seem to be producing good results (OXAL, 5-FU, Leucovorin, and Xeloda). Are those pretty standard or are there others that I should be considering if I choose the chemo route.
Suggestions welcome.
C
PS: you can find details about the study at ClinicalTrials.gov #NCT02008656
5/13 RCa Stage I, Age 51
Naturopathic care
10/14 CEA 4.9
1/15 CEA 4.6
6/15 CEA 3.8
7/15 IMRT + Xeloda (6 weeks)

Ktwirls
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Location: Quad Cities IA/IL
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Re: Prospective Phase II US study: complete clinical respond

Postby Ktwirls » Tue Feb 03, 2015 1:54 am

I would be wary to see the watch and wait approach become the standard of care. I want people to have an informed decision about both approaches. Just a fyi I was T4 which was outside the recommended watch and wait, most are T2 and some T3. I felt I did extremely well considering I was so far out of that. I had tried to get a "better" biopsy like weissoccermom talks about but couldn't get them to do that so I was only able to get "surface" biopsy when I had my follow ups. For me, my decision wasn't purely medical it was also taking in account all the things in my life that drs (rightly so) don't take in account when giving the current standard of care. Another thing I was told by that first dr was I wouldn't be able to have surgery if it came back. Study show the vast majority are able to have surgery if it comes back. I think people who chose to opt out of surgery have to be mentally ready (as much as you can) for it to come back and take responsibility in their choice. With me being T4 and having had the cancer for more than a year undiagnosed I had felt like it already had a chance to spread (lung/liver) and wanted quality. My quality definition and that priority of it may be different than others. Again, it just must come down to people having informed choices. I guess that to me is so important and I like making my own informed decisions about my life. My current onc dr agrees with informed decision making and laying all the choices out.
Kim Ann, mom to 6
dx May 2010 age 37 (symptoms started in pregnancy age 36)
Rectal Cancer stage 3b T4,N1
FolFox 8, chem/rad 6wks
It came back March 2014
APR w/ PPE surgery, now on chemo, latest scan NED
http://cancercaughtme.blogspot.com/

Ktwirls
Posts: 147
Joined: Thu Aug 12, 2010 9:12 am
Location: Quad Cities IA/IL
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Re: Prospective Phase II US study: complete clinical respond

Postby Ktwirls » Tue Feb 03, 2015 2:02 am

Interesting that the ClinicalTrials.gov #NCT02008656 is having two arms 1) chemo first, then rad/chemo or 2) rad/chemo first, then chemo. I did chemo first, then the rad/chemo same chemo drugs they list. I wonder if having one of them first makes a huge difference since both arms it is the same but just different order. Also, they are including T3 and T4 and node positive.
Kim Ann, mom to 6
dx May 2010 age 37 (symptoms started in pregnancy age 36)
Rectal Cancer stage 3b T4,N1
FolFox 8, chem/rad 6wks
It came back March 2014
APR w/ PPE surgery, now on chemo, latest scan NED
http://cancercaughtme.blogspot.com/

weisssoccermom
Posts: 5962
Joined: Thu May 10, 2007 2:32 pm
Location: Pacific NW

Re: Prospective Phase II US study: complete clinical respond

Postby weisssoccermom » Tue Feb 03, 2015 2:24 am

IMO, in addition to being mentally prepared should the cancer recur, I also believe that patients who undergo the full thickness excision (whether the 'regular' excision or the TEM) MUST be prepared to make a decision should the pathology report come back showing cancer cells deeper in the rectal wall. Personally, I also feel that a total 'wait and see' approach, with the benefit of adjuvant chemo....especially for stage II and above......is a little risky. The model I followed was as follows:

chemoradiation
surgery
chemo

Now, I reversed order on the last two and still would have done more chemo had the pathology report not come back totally clear. I'm just not sure that I would be comfortable with chemoradiation only with or without an excision.
Dx 6/22/2006 IIA rectal cancer
6 wks rad/Xeloda -finished 9/06
1st attempt transanal excision 11/06
11/17/06 XELOX 1 cycle
5 months Xeloda only Dec '06 - April '07
10+ blood clots, 1 DVT 1/07
transanal excision 4/20/07 path-NO CANCER CELLS!
NED now and forever!
Perform random acts of kindness


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