The Doctor's Channel - Oncology

Fertility-conserving surgery safe for early cervical cancer

2010-03-09T16:57:54+00:00

NEW YORK (Reuters Health) – In young women with stage IA1 cervical cancer, a fertility-preserving conization does not reduce survival compared to hysterectomy, researchers report in the March Obstetrics and Gynecology.

With either procedure, 5-year survival is excellent, approaching 100%, the findings indicate.

Small series and case control studies have suggested that conization is safe, but large studies comparing conization and hysterectomy for stage IA1 cervical cancer have been lacking until now, according to lead author Dr. Jason D. Wright, from Columbia University College of Physician and Surgeons, New York, and colleagues.

For the current analysis, the researchers used data from the Surveillance, Epidemiology, and End Results database from 1988 to 2005. They identified 1409 women, age 40 or younger, with stage IA1 cervical cancer; 841 had hysterectomy and 568 underwent conization.

On logistic regression analysis, predictors of conization included Asian ethnicity, single status, diagnosis later in the study period, and residence in the eastern United States. In addition, women younger than 30 had a 78% higher likelihood of conization compared to women above 35.

At 5 years, 98% of those treated with conization and 99% treated with hysterectomy were alive.

“Our study suggests that fertility-conserving surgery is safe for young women with stage IA1 squamous cell carcinoma of the cervix,” the authors conclude. “Young women with microinvasive cervical tumors should weigh the risks and benefits of conization in the context of individual preferences and tumor characteristics.”

Reference:
Obstet Gynecol 2010;115:585-590.

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Prostate cancer prevention and nutrition

2010-03-08T15:39:19+00:00

David Heber, MD, Professor of Medicine, Director, UCLA Center for Human Nutrition, discusses prostate cancer prevention, and explains why low fat diets and exercise can reduce inflammation by reducing the amount of circulating cytokines and thereby help prevent this common male cancer.

Reading:
Freedland SJ, Aronson WJ. Dietary intervention strategies to modulate prostate cancer risk and prognosis. Curr Opin Urol. 2009 May;19(3):263-7. Review.
Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Weiss N, Goodman P, Antvelink CM, Penson DF, Thompson IM. Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial.
Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV, Thun MJ, Calle EE. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):63-9. Epub 2006 Dec 19.

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Prophylactic mastectomy may slightly improve survival in young breast cancer patients

2010-03-03T16:10:33+00:00

NEW YORK (Reuters Health) – Contralateral prophylactic mastectomy slightly improves breast cancer-specific survival, primarily in young women with early-stage estrogen receptor (ER)-negative disease, new research shows.

“The efficacy of prophylactic mastectomy in reducing the incidence of breast cancer is well established,” Dr. Isabelle Bedrosian and co-authors, from the M.D. Anderson Cancer Center, Houston, note. However, “the potential benefit of contralateral prophylactic mastectomy in reducing breast cancer mortality has not been adequately studied.”

To investigate, the researchers analyzed data from the Surveillance, Epidemiology, and End Results database on 107,106 women who had mastectomies between 1998 and 2003. This cohort included 8902 women who had the contralateral breast removed as well, according to the report in the February 25th online issue of the Journal of the National Cancer Institute.

On initial analysis, contralateral prophylactic mastectomy was associated with a 37% reduced risk of death from breast cancer (p < 0.001). Further investigation showed that this was driven by a reduction in breast cancer–specific mortality in the subset of 4854 women aged 18 to 49 years with stage I/II ER-negative cancer (hazard ratio, 0.69).

Without mastectomy of the other breast, 5-year adjusted breast cancer-specific survival was 83.7%; with contralateral mastectomy, the rate climbed slightly to 88.5%.

In the women with early stage disease who did have the second breast removed, rates of metachronous primary cancer in the contralateral breast did not differ significantly by ER status.

Without a contralateral prophylactic mastectomy, however, 44 of 4854 (0.90%) young women with ER-negative tumors developed a cancer in the second breast at a median follow-up of 47 months, compared to 53 of the 11,585 young women (0.46%) with ER-positive tumors (p < 0.001).

There was no indication that contralateral prophylactic mastectomy improved the survival of patients over 60 years of age, regardless of disease stage and ER status. “Breast cancer patients over the age of 60 can be reassured that they will not benefit from CPM,” Dr. Bedrosian said in a statement.

“However, there are other populations—such as women between the age of 50 and 60—where the findings about the procedure remain less clear,” she said. Similarly, the benefit of CPM for young women with early stage, ER-positive breast cancer who receive tamoxifen for only 5 years needs to be clarified.

Reference:
J Natl Cancer Inst 2010.

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Chromocolonoscopy not helpful for routine colon cancer screening

2010-03-02T16:00:45+00:00

NEW YORK (Reuters Health) - Although high-definition chromocolonoscopy may detect some adenomas missed with standard high-definition colonoscopy, it should not be used for routine colon cancer screening in average-risk patients, new research suggests.

The newer technology slightly improved detection of flat and small adenomas, but it was similar to standard high-definition white light colonoscopy for detecting advanced neoplasms, according to the February 23rd online report in The American Journal of Gastroenterology.

The improved detection rates reported with high-definition chromocolonoscopy have come from studies in patients at increased risk for colorectal neoplasms, lead author Dr. Charles J. Kahi, from Indiana University School of Medicine, Indianapolis, and associates note. Whether this modality offers any benefit in average-risk patients, however, is unclear.

To investigate, the researchers randomized 660 average-risk patients to undergo either high-definition chromocolonoscopy or white-light colonoscopy at four centers in the US.

Nearly 55% of patients evaluated with chromocolonoscopy had at least one adenoma compared with 48.4% assessed with white light colonoscopy. The number of adenomas per patient was also slightly higher in the chromocolonoscopy group: 1.3 vs. 1.1. Neither of these differences was statistically significant.

Both methods were comparable in detection of advanced neoplasms. One invasive malignancy was detected in each group, neither of which was a flat adenoma.

Chromocolonoscopy detected significantly more small (<5 mm) adenomas per patient (0.8 vs. 0.7) and more flat adenomas (0.6 vs. 0.4) than did white light colonoscopy, but the absolute difference was small.

"Given the small magnitude and uncertain clinical significance of the differences, our findings do not support the routine performance of high-definition chromocolonoscopy for colorectal cancer screening in average-risk patients," the authors conclude.

Reference:
Am J Gastroenterol 2010.

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Nutrition, breast cancer and prevention

2010-02-24T16:48:27+00:00

David Heber, MD, Professor of Medicine, Director, UCLA Center for Human Nutrition, discusses nutrition in breast cancer, and the role of diabetes and obesity in post-menopausal breast cancer, ie breast cancer in women over 50, which accounts for more than 75 percent of all female breast cancer cases. He also discusses breast cancer prevention starting with weight loss.

Reading:
Anderson AS, Caswell S. Obesity management--an opportunity for cancer prevention. Surgeon. 2009 Oct;7(5):282-5.
Schlienger JL, Luca F, Vinzio S, Pradignac A. [Obesity and cancer] Rev Med Interne. 2009 Sep;30(9):776-82. Epub 2009 Jun 12. Review. French.
Howell A, Chapman M, Harvie M. Energy restriction for breast cancer prevention. Recent Results Cancer Res. 2009;181:97-111. Review.

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Is laparoscopy feasible for early gallbladder cancer?

2010-02-18T20:17:50+00:00

NEW YORK (Reuters Health) – In selected patients with suspected early-stage gallbladder carcinoma, laparoscopy is a safe approach, Korean physicians report in the February Archives of Surgery.

“Although laparoscopic surgery is widely applied in a variety of malignant diseases, such as colon cancer, gastric cancer, and hepatoma, its application to gallbladder malignancy was not tried before, so it is considered ‘taboo,’” lead author Dr. Ho-Seong Han from Seoul National University Bundang Hospital told Reuters Health by email.

As long as oncologic principles are observed, however, “including radical resection of tumor and adequate lymph node dissection, there is no reason” that laparoscopy can’t be used for gallbladder cancer, Dr. Han added.

If the gallbladder disease turns out to be benign, patients will have been spared unnecessary open surgery, according to Dr. Han and colleagues. Even with malignant disease, they note, lymphadenectomy can be done laparoscopically, for a less invasive procedure.

In the same issue of the journal, however, Dr. Jeffrey B. Matthews from the University of Chicago argues in an invited critique that this approach is too risky. Dr. Matthews would rather see all patients with malignant disease undergo conversion to open operation. He worries that laparoscopic surgery increases the risk of “rendering a potentially curative situation incurable through operative error or inadequate tumor clearance.”

For their prospective study, Dr. Han and colleagues considered 36 patients with suspected gallbladder carcinoma at stage T2 or less, without evidence of liver invasion on computed tomography. Three patients had liver involvement revealed by endoscopic ultrasound, which ruled out laparoscopy. Another 3 had hepatic involvement on ultrasonography at the start of laparoscopy, so their surgeries were converted to open procedures.

In the remaining 30 patients, the course of surgery was based on results of intraoperative frozen biopsy. Twelve patients whose frozen sections suggested benign disease had laparoscopic cholecystectomy only. Pathology reports later showed that 2 patients had T1a carcinoma, for which cholecystectomy is considered definitive treatment.

For the 18 patients with malignant disease, the authors write, “The gallbladder, including about 2 mm of the thin liver tissue adhered to the gallbladder, was carefully resected so as not to spill the potentially malignant bile and not to expose the subserosal layer of the gallbladder…. Once the specimen had been completely detached, it was inserted into a protective bag and extracted through the umbilical port site.” This procedure was followed by locoregional laparoscopic lymphadenectomy.

There were no bile spills due to gallbladder perforation, the authors report. Median operative time for carcinoma cases was 190 minutes, and median blood loss was 50 mL. Tumors ranged from 1.4 to 7.5 cm. None of the patients required repeat resection, although 10 had stage pT2 carcinoma. Median postoperative stay was 4 days.

At a median follow-up of 27 months, all 18 cancer patients were alive without recurrence or port site metastasis.

“We are still accumulating cases at about 5 or 10 a year, therefore, totaling more than 50 cases,” Dr. Han told Reuters Health. “Among the patients who underwent this operation, all the patients survived until now, with only one recurrent case. When compared with open surgery, our survival result is good, considering the prognosis of T2 gallbladder cancer is poor.”

Two patients had complications during lymphadenectomy: a hemorrhage from a torn branch of the main portal vein, which required conversion to laparotomy, and a bile duct injury that was repaired laparoscopically.

Three postoperative complications – symptomatic fluid collection at the gallbladder fossa, transient blood drainage from an indwelling drain, and voiding difficulty – were successfully handled without radiologic intervention or reoperation.

In his comments to Reuters Health, Dr. Han pointed out that the ideal candidate for laparoscopic surgery is someone suspected of having early gallbladder cancer (stage T2 or lower). However, “if tumor has invaded the liver or the gallbladder serosa, open radical cholecystectomy should be considered, although laparoscopic liver wedge resection or S4b & S5 resection can be performed in the future.”

In response to Dr. Matthews’ critique, Dr. Han said, “He is right that we should be prudent when we start the new procedure. However, many new scientific developments have to get through due and sincere critics. Laparoscopic radical cholecystectomy using our technique is exactly the same as open surgery except that it is a minimal approach. The oncologic principle should be the same whether it is open or laparoscopic surgery.”

The article recommends that in the event of a positive margin of the gallbladder or cystic duct, or for surgeons lacking expertise in advanced laparoscopic dissection, laparoscopy should be converted to an open procedure for further resection and lymphadenectomy.

Also, the authors emphasize, if carcinoma is suspected prior to surgery, “one should pay as close attention as possible to not perforate the gallbladder and must use a protective bag during the extraction.”

Dr. Han and colleagues conclude that laparoscopic resection with lymphadenectomy is technically feasible and “the interim outcome is acceptable for highly selected patients who have early-stage gallbladder carcinoma without liver invasion.” They acknowledge, however, that long-term follow-up and randomized trials are needed to confirm their results.

Reference:
Arch Surg 2010;145:128-133.

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Adding cetuximab may improve treatment of lung cancer

2010-02-17T19:01:01+00:00

NEW YORK (Reuters Health) - In patients with untreated advanced non-small-cell lung cancer (NSCLC), adding cetuximab (Erbitux) to platinum-based chemotherapy can improve overall survival and response rates, a new meta-analysis suggests.

Still, for these patients, the "choice of cetuximab-chemo or chemo alone...depends on the absolute difference of clinical benefit more than whether it formally achieves statistical significance or not," the researchers emphasize.

According to their report in the online issue of Lung Cancer, patients treated with cetuximab plus chemo had significantly better overall survival (HR, 0.87, p = 0.004). In the four trials they analyzed (2 phase II, 2 phase III), median survival ranged from 8.3 to 11.9 months with cetuximab and 7.3 to 10.1 months without it.

Cetuximab also improved the overall response rate (RR, 1.19, p = 0.013), according to Dr. Xiaohua Liang and colleagues from Fudan University in Shanghai. Response rates with cetuximab ranged from 27.5% to 37%, whereas control groups had rates of 18% to 29%. Complete responses, even with cetuximab, were rare.

By contrast, cetuximab did not seem to improve 1-year survival or progression-free survival. With or without it, median progression-free survival hovered closely around 4.5 months. Three trials reported 1-year survival, which ranged from 33% to 50% with cetuximab and from 26% to 42% in controls.

The four trials included in the review and meta-analysis were identified through a search of MEDLINE and other sources and included 2018 patients with previously untreated NSCLC. Chemotherapy regimens included cisplatin plus vinorelbine in 2 trials, cisplatin plus gemcitabine in 1, and carboplatin plus paclitaxel in 1.

Grade 3/4 rash and infusion reaction were significantly more common with cetuximab, the report indicates, but were "predictable and manageable".

But "whether the difference in overall survival...has clinical significance" is not clear, the authors write.

However, they point out, "since (the) U.S. Food and Drug Administration takes overall survival as the major endpoint for cancer drug approvals and progression-free survival as surrogate for overall survival in the first-line treatment of NSCLC, our study showed that addition of cetuximab to chemotherapy may provide new opportunities for clinical treatment" of this disease.

Also unclear are the optimum duration of treatment and how to tell which patients are most likely to benefit, the authors conclude. "So far, it is difficult to determine a factor that can best predict the sensitivity of cetuximab for NSCLC."

Reference:
Lung Cancer 2010.

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Shorter radiation course for breast cancer does not impair long-term outcomes

2010-02-12T20:23:59+00:00

NEW YORK (Reuters Health) – Three weeks of hypofractionated whole-breast radiotherapy is at least as good as 5 weeks of standard radiotherapy after breast-conserving surgery for invasive cancer, as long as the surgical margins are clear and there’s no axillary node involvement, a long-term study shows.

The shorter course involves a lower total dose given in larger fractions. According to the report in The New England Journal of Medicine for February 11, the two approaches are associated with similar disease recurrence rates, toxic effects, and cosmetic outcomes at 10 years.

“Despite positive early results there was reluctance to adopt (the 3-week hypofractionated radiation) approach because of concerns regarding long-term toxicity,” lead author Dr. Timothy J. Whelan, from Juravinski Cancer Centre, Hamilton, Ontario, Canada, told Reuters Health by email. This study shows that toxicity is not increased and the shorter treatment continues to be effective, he added.

“This is a win-win situation for women with breast cancer and the health care system,” Dr. Whelan said. “Women can have a shorter more convenient treatment and it is less costly to them, and health care providers.”

He continued, “It has been suggested that some women may avoid breast-conserving surgery because of the need for lengthy radiation treatments. This may increase the attractiveness of this option by making it easier and less costly.”

Between 1993 and 1996, the 1234 women who participated in the study were randomized to receive either standard therapy (50.0 Gy in 25 fractions over 35 days) or hypofractionated therapy (42.5 Gy in 16 fractions over 22 days).

At 10 years, the risk of local recurrence was 6.2% with the hypofractionated regimen compared with 6.7% with the standard regimen. Ten-year survival rates were 84.6% with the hypofractionated regimen and 84.4% with the standard regimen.

There was no significant difference between the groups in late toxic effects on skin or subcutaneous tissue. Likewise, the percentage of subjects with a good or excellent cosmetic outcome at 10 years, based on nurse ratings, was comparable in each group: 69.8% with the hypofractionated regimen vs. 71.3% with the standard protocol.

(Just last week in The Lancet Oncology, UK researchers reported on similar patients who participated in the randomized START trials. At 5 years after treatment, there were lower rates of moderate or marked change in skin appearance, breast shrinkage and hardness, and other breast symptoms with hypofractionated radiotherapy vs the standard course. See Reuters Health story posted October 8, 2009.)

“Based on these positive results we are now exploring an even shorter treatment given over just one week,” Dr. Whelan said. “Over 1500 Canadian women are enrolled in the RAPID trial and it will continue to enroll a total of just over 2100 women. In this study radiation is limited to just the part of the breast involved with cancer. This is likely to further reduce the inconvenience of treatment and may decrease toxicity associated with radiation to improve the quality of life of women with breast cancer.”

Reference:
N Engl J Med 2010;362:513-520.

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Paroxetine limits the benefit of tamoxifen for breast cancer survival

2010-02-12T20:14:45+00:00

NEW YORK (Reuters Health) - Use of paroxetine during tamoxifen therapy reduces the breast cancer survival benefit by 25% or more depending on the amount of time the drugs are used together, according to a report in the February 9th Online First issue of BMJ.

Prior research has shown that by blocking cytochrome P450 2D6, paroxetine can reduce the metabolism of tamoxifen to its active form. However, "there have been no previous studies examining mortality, and most of what is published involves surrogate outcomes or small sample sizes," study co-author Dr. David N. Juurlink, from Sunnybrook Health Sciences Center, Toronto, told Reuters Health by email.

According to the report, there is no evidence that paroxetine has any direct effect on the clinical course of breast cancer. Rather, it simply makes tamoxifen less effective than it otherwise would be. Thus, a paroxetine user on tamoxifen is still likely to fare better than one not taking tamoxifen, although this was not the focus of the current study.

Use of other selective serotonin reuptake inhibitors (SSRIs) did not affect breast cancer mortality in tamoxifen users. Exactly why this was the case for fluoxetine, which is also a strong inhibitor of cytochrome P450 2D6, is unclear and will require further study.

The take-home message is that if an SSRI is needed in a woman who will be using tamoxifen, there are better choices than paroxetine, such as venlafaxine and citalopram, Dr. Juurlink said. He emphasized, however, that tamoxifen users already taking paroxetine "should absolutely not stop paroxetine suddenly based on these results."

The findings stem from a cohort study of 2430 women living in Ontario, Canada, who were 66 years of age or older and were treated with tamoxifen between 1993 and 2005. The median age in the year before tamoxifen was started was 74 years. At some point during tamoxifen therapy, each woman was also treated with a single SSRI, including paroxetine, fluoxetine, sertraline, fluvoxamine, citalopram, or venlafaxine (a serotonin-norepinephrine reuptake inhibitor).

During a mean follow-up period of 2.38 years, 374 women (15.4%) died from breast cancer.

On multivariate analysis, the duration of overlap between tamoxifen and paroxetine use was directly related to the risk of death from breast cancer. As the proportion of time with overlap increased from 25% to 50% and 75%, the relative risk of death from breast cancer climbed from 24% to 54% and 91%, respectively (p < 0.05 for each).

The authors calculate that if paroxetine were used during 41% of the course of tamoxifen therapy -- the median overlap period in the study -- then one extra breast cancer death would occur within 5 years of stopping tamoxifen for every 19.7 patients treated.

Furthermore, using paroxetine for 100% of the time on tamoxifen would result in one extra death for every 6.9 treated patients, compared to a setting in which the two drugs overlapped for only 1% of the time.

As noted, overlap with other SSRIs and tamoxifen did not seem to influence breast cancer mortality.

Dr. Frank Andersohn, co-author of an accompanying editorial, told Reuters Health by email that the findings are consistent with the known drug interactions between tamoxifen and paroxetine. However, "it remains unclear how to interpret the rather unexpected finding of no increased risk for fluoxetine. For safety reasons, it seems safer also to avoid fluoxetine in combination with tamoxifen."

"It seems important to further study the impact of concurrent treatment with fluoxetine. If the finding of an increased risk with paroxetine, but not with fluoxetine, is replicated in additional studies, one should further try to identify the reasons for this heterogeneity," according to Dr. Andersohn, a senior research associate with Charite University Medical Centre, Berlin.

Reference:
BMJ 2010.

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Simple ovarian cysts not linked to cancer in postmenopausal women

2010-02-05T20:30:13+00:00

NEW YORK (Reuters Health) - In women over 55, simple ovarian cysts are common, usually resolving or persisting without progression, according to data from the prospective Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

The presence of simple cysts, often found incidentally during transvaginal ultrasound (TVU) exams, did not affect the risk of ovarian cancer, according to lead author Dr. Robert T. Greenlee and colleagues -- bolstering recent recommendations that unilocular simple cysts in postmenopausal women be followed without intervention.

Dr. Greenlee, from the Marshfield Clinic Research Foundation, Wisconsin, and associates followed 15,735 postmenopausal women through 4 years of annual TVU screening. All were between 55 and 74 years old at enrollment, and all had CA-125 measurements and TVU studies at baseline. Both tests were repeated annually. In addition, for a woman to be included in the study, both ovaries had to be visualized at least once by TVU.

Simple cysts were defined as having a volume < 10 cm3 and with no solid areas, septae, or papillary projections within the cyst cavity.

In a paper published online January 25 in the American Journal of Obstetrics and Gynecology, the investigators report that the prevalence of at least 1 simple cyst detected during the first fully visualized TVU screening was 14.1%. Potential correlates of prevalent simple cysts were younger age (55 to 59), education past high school, and early menopause. The odds were also higher in women with a history of benign ovarian cysts, menopause before age 40, and a first pregnancy at or beyond age 30.

Among women without a cyst of any kind on their first fully visualized TVU screening, the incidence of simple cysts was approximately 8% per year, remained fairly constant, and did not vary by age.

One-third of ovaries with simple cysts were cyst-free the following year. Even when 2 or more cysts were present, all resolved a quarter of the time. Only 6% progressed in complexity from 1 year to the next.

Women with and without simple cysts were at similar risk of invasive ovarian cancer after nearly 8 years of follow-up evaluation, the authors write. Furthermore, traditional ovarian cancer risk factors, such as increasing age, family history of breast or ovarian cancer, nulliparity, and infertility, were not associated with simple cysts. Finally, changes in average CA-125 were not correlated with increases in the number or progression of simple cysts.

Thus, Dr. Greenlee and his group conclude, “Simple cysts are not likely cancer precursors or markers of increased risk and can be followed conservatively.”

Reference:
Am J Obstet Gynecol 2010.

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