PCI debate? And a poll...

[gerbil runner]

My mom is trying to decide whether or not to have PCI. One onc. is in favor, the other is strongly opposed, saying he has seen several cases of serious mental impairment.

To make matters more complicated, if my mom does the stem-cell treatment, one of the drugs they plan to use is supposed to cross the blood-brain barrier.

I've done a couple of google searches, but none of the info seems terribly recent, nor do the studies have much to say about long-term results beyond 2-3 years. Anybody heard anything recent?

Maybe a poll is a good place to start. If you're a family member or caretaker, your input is welcome, too.

[MO_Sugar]

I had PCI after I reached "Stable" and had completed the radiation to my chest. I have not noticed any long term side effects other than it is hard once in awhile to come up with a word (could be older age setting in also, lol). My hair had started to come in after chemo (white) and I lost it all again during PCI, it is now coming in black???? Other than that I don't see any long term effects. Short term was fatigue, a "peeling" head for about 2 weeks and thats about all I had. I was of the mind that if it offered me even a few more months I would go for it. Your Mom will have to decide and maybe it is something they can look at after the stem cell???

Best wishes on a tough decision.

God Bless,

MO

[betplace]

I will be interested in everyones reply's. My oncologist does not recommend PCI for extensive stage patients like me. I am not sure if I am happy or upset about that.

blessings

Betty

[john]

I think it is standard NOT to recommend PCI for extensive stage patients.

If you search this site, that is what Dr Sam said in his posts. PCI results in a about a 5% decrease in mets (I think this is the right number). One study said that women benefit more.

http://www.guideline.gov/summary/summar ... oc_id=3651

If you look at the above evidence based guidlines: It gives a grade of C for extensive stage patients, but a grade of A for limited stage with complete remission

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Mayo Clin Proc. 1999 May;74(5):461-5. Related Articles, Links

Cerebral toxicity in patients treated for small cell carcinoma of the lung.

Fonseca R, O'Neill BP, Foote RL, Grill JP, Sloan JA, Frytak S.

Division of Medical Oncology, Mayo Clinic Rochester, Minnesota 55905, USA.

OBJECTIVE: To present the clinical characteristics of patients enrolled in a trial of treatment of small cell carcinoma (SCC) of the lung and to describe the central nervous system toxicity associated with the chemotherapy and prophylactic cranial irradiation (PCI). MATERIAL AND METHODS: We performed a retrospective analysis of 60 patients with SCC who received chemotherapy and thoracic radiation therapy. PCI was administered to patients who had limited disease or who had extensive disease that was subsequently down-staged to only residual chest disease after initial treatment. The total PCI dose was 3,200 cGy administered in 16 fractions of 200 cGy, given concurrently with systemic chemotherapy. Diagnostic criteria for leukoencephalopathy were based on previously published guidelines. RESULTS: Of the 60 eligible and enrolled patients, 35 received PCI and 25 did not. Leukoencephalopathy developed in 5 of the 35 patients (14%) who received PCI. The median age of the patients in whom leukoencephalopathy developed was 64 years (range, 57 to 69), and the median follow-up time was 59 months. The most common signs and symptoms of leukoencephalopathy were intellectual changes, memory alterations, and motor abnormalities. The mean time to onset of symptoms after termination of irradiation was 357 days (range, 30 to 524). Of all 60 patients, 6 were still alive 4 years after enrollment, and 3 of them (50%) already had leukoencephalopathy. CONCLUSION: Small dosage fractions of PCI may still result in leukoencephalopathy. The routine use of PCI in the management of SCC should be reassessed because of increasing evidence of the toxicity associated with it.

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Abstract

Background: Prophylactic cranial irradiation (PCI) as part of the treament regimen for patients with limited stage small cell lung cancer (SCLC) remains controversial. The present study was performed to analyze the efficacy and safety of PCI in patients with limited stage SCLC who achieved complete remission. Patients and methods: Between 1983 and 1993, thirty-nine patients with limited stage SCLC who had shown complete remission after chemotherapy were enrolled prospectively into the non-randomized study. Eighteen of them received PCI (PCI+), while 21 did not (PCI−). Pretreatment CT or MRI of the brain was performed in all patients. Patients were prospectively evaluated by a neurologist at regular intervals. Results: Three PCI+ patients and seven PCI− patients developed brain metastases. The frequencies of brain metastases were not significantly different between the groups (Fisher‘s exact test, p = 0.207), but brain metastases in PCI+ patients tended to occur later (log rank, p=0.008). Overall survival was significantly longer in PCI+ patients (log rank, p < 0.001). Early toxicity consisted of headache, nausea, fatigue, concentration problems and alopecia. These symptoms and signs were mild and usually reversible within a few months. Late toxicity was studied in patients whose survival exceeded two years. Seven PCI+ patients survived for more than two years, while no PCI− patients survived for more than two years. Memory problems were seen in six of the seven patients. These problems were non-disabling and, once established, remained stable for months to years. The most prominent radiologic abnormalities were cortical atrophy and leukoencephalopathy, found in four of the five patients who underwent radiologic follow-up examination. Conclusions: This non-randomized study suggests that PCI may be effective by decreasing the frequency of brain metastases and by increasing the brain metastasis-free survival and overall survival, with a minor risk of clinical and radiologic neurotoxicity.

Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer in Complete Remission. Prophylactic Cranial Irradiation Overview Collaborative Group

Auperin A, Arriagada R, Pignon JP, et al.

N Engl J Med. 1999;341:476-484.

Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival.

We analyzed individual data on 987 patients with small-cell lung cancer who were in complete remission and who had taken part in 7 trials that compared outcomes of patients receiving prophylactic cranial irradiation with those who did not receive prophylactic cranial irradiation. The main end point was survival.

The relative risk of death in the treatment group, compared with the control group was 0.84 (95% CI, 0.73 to 0.97; P=.01), which corresponds to a 5.4% increase in the rate of survival at 3 years (15.3% in the control group vs 20.7% in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95% confidence interval, 0.65 to 0.86; P<.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95% confidence interval, 0.38 to 0.57; P<.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of 4 total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy.

Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.

Does Prophylactic Cranial Irradiation for Patients With Limited Small-Cell Lung Cancer Improve Survival?

Editorial Comment by Ritsuko Komaki, MD, FACR

Key Words:

Limited small-cell lung cancer

Prophylactic cranial irradiation (PCI)

Brain metastasis

Combined chemotherapy with thoracic radiation therapy for patients with limited small-cell lung cancer has resulted in longer survival for patients who have achieved complete response.[1-3] With the prolongation of survival, however, brain metastasis has became a serious problem.[4-5] Nugent and colleagues[6] reported cumulative probability of the CNS metastasis up to 80%, including extracranial CNS metastasis for patients who lived long enough. To reduce the incidence of intracranial brain metastasis, prophylactic cranial irradiation (PCI) was initiated during the 1970s, since it was recognized that subclinical metastases were protected from cytoxic drugs by the blood-brain barrier[7] and that elective brain irradiation (EBI) was assumed to prevent the development of clinically metastatic growth. Several randomized trials revealed that PCI was effective in reducing the incidence of brain metastasis.[8-14] However, longer-term survival and sophisticated MRI findings revealed neurotoxicity from PCI and neurotoxic drugs.[15-19]

These findings led to neuropsychological testing,[5,20-21] which showed no significant deterioration of the neuropsychological function after PCI compared with baseline evaluation. Komaki and colleagues[21] found significant cognitive deficiency among the patients with limited small-cell lung cancer before any treatment, which suggests that a possible cause for their cognitive deficiency correlated with paraneoplastic syndrome. Because of the lack of significant benefit to improve overall survival, some oncologists refrained from using PCI, even for patients with limited small-cell lung cancer in complete remission. However, the meta-analysis by Auperin et al[22] showed significantly improved overall survival rates for patients who received PCI after complete remission.

The strength of this paper is the large sample size from the 7 trials that looked at the benefit of PCI in 987 patients with limited small-cell lung cancer who achieved complete remission. The clinical trials observed strict inclusion criteria. Results showed a relative risk of death in the treatment group of 0.84 (95% confidence interval, 0.73 to 0.97; P=.01). This means that PCI improved overall survival from 15.3% to 20.7% in 5 years. In addition, brain metastasis-free survival improved among the patients who received PCI from 13.5% to 22.3% in 5 years (P=.001). PCI reduced the cumulative incidence of brain metastasis from 59% to 33% (P>.001). Doses of PCI ranging from 8 Gy to 40 Gy were compared. The decrease of relative risk (RR) of brain metastasis was 0.76 by 8 Gy, 0.52 by 24 to 25 Gy, 0.34 by 30 Gy, 0.27 by 36-40 Gy (P=.02), although there was no significant improvement in the survival by increasing the total dose of PCI. The time between the start of induction therapy and randomization for PCI showed significant reduction of RR of brain metastasis favoring a shorter interval of less than 4 months (0.27), 4 to 6 months (0.5), or longer than 6 months (0.69) (P=.01). Among 350 patients who had pre- and posttreatment neuropsychological analysis, no signficant neuropsychological deterioration by the application of PCI was seen.

The weakness of this paper is that the multicenter studies occurred over different time periods (from 1965 through 1995) and used various imaging studies for staging and workup. Different types of chemotherapeutic agents as well as different radiation treatments were used. Also, only 67% of patients were available for analysis of locoregional occurrence and distant metastasis. This challenges interpretation of CNS failure in cases in which PCI is ineffective or related to reseeding.

Despite the lack of standardization, this meta-analysis shows for the first time the effectiveness of PCI in patients who achieved complete response after combined chemo- and thoracic radiation therapy to improve overall survival with no significant deterioration of the neuropsychological function. In the future, patients with limited small-cell lung cancer should be tested before treatment for any significant cognitive dysfunction related to paraneoplastic syndrome. Patients who achieve complete response should receive PCI within a short interval, either after completion of systemic treatment or an early course of treatment.

References

Albain KS, Browley JJ, LeBlanc M, Livingston RB. Determinants of improved outcome in small-cell lung cancer: an analysis of the 2,580-patient Southwest Oncology Group database. J Clin Oncol. 1990;8:1563-1574.

Arriagada R, Kramar A, LeChevalier T, DeCremoux H. Competing events determining relapse-free survival in limited small-cell lung carcinoma. J Clin Oncol. 1992;10:447-451.

Turrisi AT III, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340:265-271.

Komaki R. Prophylactic cranial irradiation for small cell carcinoma of the lung. Cancer Treat Symp. 1985;2:35-39.

Arriagada R, LeChevalier T, Borie F, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst. 1995;87:182-190.

Nugent MJ, Bunn PA, Matthews MJ, et al. CNS metastases in small cell bronchogenic carcinoma. Cancer. 1979;44:1865-1893.

Hansen HH. Should initial treatment of small cell carcinoma include systemic chemotherapy and brain irradiation? Cancer Chemotherapeutic Rep. 1973;4:239-241.

Cox JD, Stanley K, Petrovich Z, et al. Cranial irradiation in cancer of the lung of all cell types. JAMA. 1981;245:469-472.

Beiler DD, Kane RC, Bernath EM, et al. Low dose elective brain irradiation in small cell carcinoma of the lung. Int J Radiat Oncol Biol Phys. 1979;5:944-945.

Aisner J, Whitacre M, Van Echo DA, et al. Combination chemotherapy for small cell carcinoma of the lung: continuous vs alternating non-cross resistant combinations. Cancer Treat Rep. 1982;66:221-230.

Jackson DV, Richards F, Cooper MR, et al. Prophylactic cranial irradiation in small cell carcinoma of the lung: a randomized study. JAMA. 1977;237:2730-2733.

Maurer LH, Tulloh M, Weiss RB, et al. A randomized combined modality trial in small cell carcinoma of the lung: comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactic whole brain irradiation. Cancer. 1980;45:30-39.

Seydel HG, Creech R, Pagano M, et al. Combined modality treatment of small cell undifferentiated carcinoma of the lung: a cooperative study of the RTOG and the ECOG. Int J Radiat Oncol Biol Phys. 1981;7:41.

Hirsch FR, Hansen HH, Paulson OB, et al. Development of brain metastases in small cell anaplastic carcinoma of the lung. In: Kay J, Whitehouse J, eds. CNS Complications of Malignant Disease. New York: MacMillan; 1979:175-184.

Carane R, Schwade JG, Yarr I, et al. Follow-up and neurological evaluation in patients with small cell lung carcinoma treated with prophylactic cranial irradiation and chemotherapy. Int J Radiat Oncol Biol Phys. 1981;7:105-109.

Johnson BE, Patronas N, Hayes W, et al. Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol. 1990;8:48-56.

Lee JS, Umsawadi T, Lee YY, et al. Neurotoxicity in long-term survivors of small cell lung cancer. Int J Radiat Oncol Biol Phys. 1986; 12:313-321.

Lishner M, Feld R, Payne DG, et al. Late neurological complications after prophylactic cranial irradiation in patients with small-cell lung cancer: the Toronto experience. J Clin Oncol. 1990;8:215-221.

Frytak S, Shaw JN, O'Neill BP, et al. Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation. Am J Clin Oncol. 1989;12:27-33.

Gregor A, Cull A, Stephens RJ, et al. Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. Eur J Cancer. 1997;33:1752-1758.

Komaki R, Meyers CA, Shin DM, et al. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys. 1995;33:179-182.

Auperin A, Arriagada R, Pignon J-P, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999;341:476-484.

Abstr Hematol Oncol 3(2):17-18, 2000. © 2000 Cliggott Publishing, Division of SCP Communications

[gerbil runner]

Thanks, John, for your quotes. It always amazes me, the way you find this stuff!

My mother's case is somewhat unique. She has extensive SCLC, but only 2 sites - lung and pancreas. She also has a complete response to chemo.

So her oncologist, after consulting with a collegue in Colorado, sent her on to radiation, treating both original tumor sites.

If she does have the PCI, it will be after the stem-cell (assuming she has that).

I'm really interested in finding out the possible long-term consequences of PCI, and how severe they might be. Mom's worried about compromising quality of life, but she certainly doesn't want to be left vulnerable. One thing that worries me is the thought of having the PCI and then getting the brain mets anyway. If 60% of patients suffer brain mets, and PCI reduces the risk by 50%, that leaves 30% of patients who are still going to get brain mets. Is it more difficult to treat the brain mets if PCI has been done?

[Cindy RN]

My oncologist did not rec. it but the radiologist did. I did some checking and decided it was not worth the risk for me. I had hoped to go back to work and as an RN in the ER I did not want to chance the memory loss I still am not able to get back to work due to shortness of breath etc. The Dr said if it mets to the brain then we could do the radiation and so far it has not.

Cindy

[SandyS]

My doctor wanted me to have PCI - and I was struggling with whether to accept it - but when the time came, they weren't sure I was in remission, so they withdrew the option. (I've been in remission for over a year now - ha!)

I was leaning towards refusing it anyway - from everything I read at the time, it seemed that the risks were too high for very little return, and they told me that if it DID happen to turn up in my brain after that, they wouldn't be able to administer as much radiation....

Good luck to all of you struggling with these kinds of tough choices!

Hugs and prayers,

SandyS

[Roseymac]

I think I had posted this before but here is what happened to my Husband. Our Onc was pretty insistant he receive PCI we struggled with it for two weeks read everything we could and decided he would go for it.

When we went to the Radiation Onc she was very hesitant and spoke with us frankly that they usually only do it for limited small cell. Her theory being that by doing low dose PCI if he does get Brain Mets, the radiaiton will not be as effective. It is easier to go after the mets when and if they come and if we had PCI we couldn't treat as aggresively She also told us that chanches for Brain Mets were 1 in 2, not very good odds, and that low dose Radiation may bring them out. So in other words she was saying don't fix it unless it's broke. I would talk to the Doctors about the issues and make your decision with Him.

Rosemary

[Connie B]

A Good Friend of mine, had SCLC Exten, (to the liver) and she had PCI and she will be a 5 year survivor come May. She has NO side effects from it and she said she would do it again. She was 64 or 65 yrs young when she had the treatments. I also have another friend SCLC Limited and she too had PCI, and she TOO said she would do it all again if she had to. She was 42 at the time and she is a 4 years survivor.

It's a HORSE A PIECE!! What works for some........ doesn't all work for others.

[OhioKat]

I had one week of PCI a year ago and while chemo only thinned my hair out the PCI took it all the way out, as well as being rather drying to my scalp. As for mental changes, I've had some but at this point even the Doc is thinking its more "chemo brain" then anything from the PCI. I guess I won't know for sure until after I've been off chemo for a while.

My Rad Docs seemed to think the PCI was the best thing to do, one even went as far as to say that he felt confident that by having it I wouldn't have to worry about a brain mets at all. Of course when they did it I was considered limited stage sclc and I probably still am, although I myself thing I was misdiagnosed at the beginning and was actually extensive because I just have a strong feeling that my ovarian tumor was there from the beginning.

Not sure if that helps you or not.

Kat

[Rachel]

Jen,

I was preparing to do PCI when the MRI showed 2 mets so I had full head radiation for 18 treatments. 2 wks after treatment I returned to Oregon for Stereotactic & found no brain mets but my Doc still did the stereo. My chest Ct was also clean so they are calling me in Remission!!

I had a tough time making the decision to have PCI. Then I didn't end up doing it. Good luck with your Mum's decision.

Rachel

[bengel]

When I went through my treatment sequence my oncologist laid out the plan in a very forthright manner and said if we are going to beat this thing then this is what we are going to do. The end treatment was PCI. I had no doughts that he was doing the best for me. I stopped by the hospital every morning for 15 days. The techs were kind enough to come in 15 minutes early so I could still get to school to teach my first period drafting class. The office staff was also helpful since I had been there for my lung radiation. I am very grateful for their support.

Bud

[Guest]

When my Dad was diagnosed with ext sclc in 1983,he had a complete response and had PCI as part of the experimental protocol he was on. He tolerated the treatments well. About 15 years into his remission he had some short term memory loss...nothing terrible in fact at that time he was about 70....was it aging or PCI or a combo...I don't know but I am certainly glad for the 20 years he had...in good health!

I realize this is anecdotal and not based on statistics...it's a tough decision...good luck.

Lynn

[john]

http://theoncologist.alphamedpress.org/ ... oncologist

[Geri]

I don't know if this will be of help, I finished my chemo in May 2002 and both of my oncologists offered me brain radiation (I had shown no tumor for several months). The onc that I trusted most gave me 40% odds that "something was lurking" in a corner of my brain so I choose to see that there was a 60% chance that there was not and didn't want to risk porrige for brains with those odds. When my decision was announced both doctors said that they were pleased but had had to offer the treatment . I've now had over 2 years of remission and no signs of any changes, due for another brain MRI in June and am keeping my fingers crossed.......... if anything shows I shall be first in line in the radiation dept!

I feel strongly that you follow your gut, I did everything that felt right to my instincts but I also had an oncologist that I trusted to tell me the truth.

good luck with your decision, unfortunately there are no easy ones.