Tuesday, February 8, 2011

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

In Cancer this week:

An interesting randomized trial looking at the use of Boswelliaserrata (an extract of Indian Frankincense) on cerebral edema, for patients undergoing radiation therapy for brain tumors (metastatic or primary). It is a modest trial with only 22pts in each arm, but they were able to demonstrate a significant decrease in T2 signal volume with the extract vs placebo. This did not however translate into a reduction in the use of steroids, nor in any clinically relevant endpoint. Of course, confirmation will be needed before this is ready for prime time, but this study is an intriguing demonstration of a novel approach at limiting steroid use.

Link and Abstract.

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: "



Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswelliaserrata (BS) in radiotherapy-related edema, we conducted a prospective, randomized, placebo-controlled, double-blind, pilot trial.


Forty-four patients with primary or secondary malignant cerebral tumors were randomly assigned to radiotherapy plus either BS 4200 mg/day or placebo. The volume of cerebral edema in the T2-weighted magnetic resonance imaging (MRI) sequence was analyzed as a primary endpoint. Secondary endpoints were toxicity, cognitive function, quality of life, and the need for antiedematous (dexamethasone) medication. Blood samples were taken to analyze the serum concentration of boswellic acids (AKBA and KBA).


Compared with baseline and if measured immediately after the end of radiotherapy and BS/placebo treatment, a reduction of cerebral edema of >75% was found in 60% of patients receiving BS and in 26% of patients receiving placebo (P = .023). These findings may be based on an additional antitumor effect. There were no severe adverse events in either group. In the BS group, 6 patients reported minor gastrointestinal discomfort. BS did not have a significant impact on quality of life or cognitive function. The dexamethasone dose during radiotherapy in both groups was not statistically different. Boswellic acids could be detected in patients' serum.


BS significantly reduced cerebral edema measured by MRI in the study population. BS could potentially be steroid-sparing for patients receiving brain irradiation. Our findings will need to be further validated in larger studies. Cancer 2011. © 2011 American Cancer Society.


Lancet: TAX 324 update

In the Lancet this week:

An update of TAX 324 is published confirming long term benefit for PFS and OS for TPF vs PF induction chemotherapy for locally advanced head and neck cancer. Clearly I think this confirms that this is the best induction regimen, however, wether induction chemotherapy is truly the best strategy remains uncertain (versus optimal up front concurrent chemo-radiotherapy), and further randomized work will be needed to establish this as the standard of care.


[Articles] Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial: "Induction chemotherapy with TPF provides long-term survival benefit compared with PF in locally advanced head and neck cancer. Patients who are candidates for induction chemotherapy should be treated with TPF."

Collins Law and Estimating a Tumors Age before diagnosis

In Oncology last week:

An interesting article from Larry Marks - which gets at a question often heard in the clinic: "How long have I had this?" Marks uses a variation on Collins Law (well described in the paper) to estimate how long a tumor may have existed from the development of the first clonogen to the time of detection based on local recurrence rates after a curative resection, and finds that some tumors may have existed for many years prior to detection (3-6 years for the sites studied).

Now obviously there are huge assumptions: first that growth rates are similar before and after a curative surgery, and it excludes tumors which may have been treated more aggressively, and recurred distantly. Therefore, one can really only apply this to low grade cancers that are likely to fail locally only. Nonetheless, it's an interesting thought experiment.

Link (requires free membership to login)

How Long Have I Had My Cancer, Doctor? - Cancer Network

How Long Have I Got? Estimating Typical, Best-Case, and Worst-Case Scenarios for Patients Starting First-Line Chemotherapy for Metastatic Breast Cancer: A Systematic Review of Recent Randomized Trials [REVIEW ARTICLE]

In the JCO:

A relatively simple way to approach estimating a patient's long term prognosis with metastatic breast cancer is put forward in the JCO this week. I liked this as it is simple, in a way that hopefully will be useful to patients when considering their prognosis, going beyond the simple median survivals that immediately come to mind. Of course, one has to take into account that these are based on published clinical trials, which tend to attract and accrue the most motivated and healthy of patients.

Link and Abstract.

How Long Have I Got? Estimating Typical, Best-Case, and Worst-Case Scenarios for Patients Starting First-Line Chemotherapy for Metastatic Breast Cancer: A Systematic Review of Recent Randomized Trials [REVIEW ARTICLE]: "Purpose

To estimate scenarios for survival for women with metastatic breast cancer (MBC) who are starting chemotherapy.

Patients and Methods

We sought randomized, first-line chemotherapy trials for MBC published from 1999 to 2009. We recorded median progression-free survival (PFS) and median overall survival (OS) and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We also estimated these scenarios for each OS curve by multiplying its median by four simple multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). Estimates were deemed accurate if they were within 0.75 to 1.33 times the actual value.


From 36 trials (13,083 women), the mean for median PFS was 7.6 months (interquartile range [IQR], 6.0 to 9.0 months), the mean for median OS was 21.7 months (IQR,18.2 to 24.0 months), and the mean for the ratio of median OS to median PFS was 3.0 (IQR, 2.4 to 3.5). The mean for each OS scenario was worst-case, 6.3 months (IQR, 4.8 to 7.5 months); lower-typical, 11.9 months (IQR, 9.9 to 13.2 months); upper-typical, 36.2 months (IQR, 31.1 to 41.3 months); and best-case, 55.8 months (IQR, 47.5 to 60.2 months). Simple multiples of the median gave accurate estimates of the worst-case scenario in 73% of OS curves, lower-typical in 97%, upper-typical in 95%, and best-case in 96%. OS was longer in trials with higher proportions of estrogen receptor–positive tumors (P = .001) and in trials of trastuzumab-treated human epidermal growth factor receptor 2–positive tumors (P = .001).


Simple multiples of an OS curve's median can accurately estimate typical (half to double the median), best-case (triple the median), and worst-case (one quarter of the median) scenarios for survival.


MDS in Atomic Bomb survivors

In the JCO:

Fortunately there are very few populations in which the late effects of single instance low dose whole body radiation can be studied. Fortunately also, the Japanese and US government have been very helpful in performing large scale studies of the long term effects of the two bombs dropped. While a fair amount of the secondary cancer risk has been published, from the data presented in JCO this week, MDS is clearly another risk that should be monitored for.

Links and Abstract:

Risk of Myelodysplastic Syndromes in People Exposed to Ionizing Radiation: A Retrospective Cohort Study of Nagasaki Atomic Bomb Survivors [Epidemiology]: "Purpose

The risk of myelodysplastic syndromes (MDS) has not been fully investigated among people exposed to ionizing radiation. We investigate MDS risk and radiation dose-response in Japanese atomic bomb survivors.

Patients and Methods

We conducted a retrospective cohort study by using two databases of Nagasaki atomic bomb survivors: 64,026 people with known exposure distance in the database of Nagasaki University Atomic-Bomb Disease Institute (ABDI) and 22,245 people with estimated radiation dose in the Radiation Effects Research Foundation Life Span Study (LSS). Patients with MDS diagnosed from 1985 to 2004 were identified by record linkage between the cohorts and the Nagasaki Prefecture Cancer Registry. Cox and Poisson regression models were used to estimate relationships between exposure distance or dose and MDS risk.


There were 151 patients with MDS in the ABDI cohort and 47 patients with MDS in the LSS cohort. MDS rate increased inversely with exposure distance, with an excess relative risk (ERR) decay per km of 1.2 (95% CI, 0.4 to 3.0; P < .001) for ABDI. MDS risk also showed a significant linear response to exposure dose level (P < .001) with an ERR per Gy of 4.3 (95% CI, 1.6 to 9.5; P < .001). After adjustment for sex, attained age, and birth year, the MDS risk was significantly greater in those exposed when young.


A significant linear radiation dose-response for MDS exists in atomic bomb survivors 40 to 60 years after radiation exposure. Clinicians should perform careful long-term follow-up of irradiated people to detect MDS as early as possible.


Results of the SPIRIT trial (Surgery vs Brachy) for Prostate

In the JCO:

Few disease sites would benefit from a randomized trial more than prostate cancer would, though we can't seem to accrue anything except for varying lengths of hormonal treatment and different postoperative strategies. The SPIRIT trial valiantly tried to correct this issue, however unfortunately failed to accrue. Fortunately, at lease some data from this attempt is published in JCO this week, and the QOL in urinary and sexual domains favor brachytherapy. Link and abstract below.

Comparison of Health-Related Quality of Life 5 Years After SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial [Urologic Oncology]: "Purpose

The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy (RP) and brachytherapy (BT) closed after 2 years due to poor accrual. We report health-related quality of life (HRQOL) at a mean of 5.3 years for 168 trial-eligible men who either chose or were randomly assigned to RP or BT following a multidisciplinary educational session.

Patients and Methods

After initial lack of accrual, a multidisciplinary educational session was introduced for eligible patients. In all, 263 men attended 47 sessions. Of those, 34 consented to random assignment, 62 chose RP, and 94 chose BT. Five years later, these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Expanded Prostate Cancer Index Composite, the Short Form 12 Physical Component Score, and Short Form 12 Mental Component Score. Response rate was 88.4%. The Wilcoxon rank sum test was used to compare summary scores between the two interventions.


Of 168 survey responders, 60.7% had BT (9.5% randomly assigned) and 39.3% had RP (9.5% randomly assigned). Median age was 61.4 years for BT and 59.4 for RP (P = .05). Median follow-up was 5.2 years (range, 3.2 to 6.5 years). For BT versus RP, there was no difference in bowel or hormonal domains, but men treated with BT scored better in urinary (91.8 v 88.1; P = .02) and sexual (52.5 v 39.2; P = .001) domains, and in patient satisfaction (93.6 v 76.9; P < .001).


Although treatment allocation was random in only 19%, all patients received identical information in a multidisciplinary setting before selecting RP, BT, or random assignment. HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction.


Wednesday, February 2, 2011

Lancet Oncology: Urorad and IMRT

A very blunt interview with Anthony Zeitman is published in Lancet Oncology, blasting the Urorad business model.

[News] US urology clinics overprescribe prostate radiotherapy: "The US Government Accountability Office is investigating allegations that urologists are reaping hundreds of millions of dollars by overprescribing intensity-modulated radiotherapy (IMRT) for prostate cancer. Since 2002, Medicare, the federal health insurance programme for elderly patients, has paid generously for IMRT—up to US$40 000 per patient."