Intentional weight loss in postmenopausal women has been found to be associated with a lower endometrial cancer risk, particularly among those with obesity, according to the results of a recent study published in the 

These findings—which draw from the Women’s Health Initiative (WHI) study data&mdash;suggest that weight loss could decrease the risk of developing endometrial cancer in postmenopausal patients by as much as 29% to 56%.

“Many older adults think it’s too late to benefit from weight loss, or think that because they are overweight or obese, the damage has already been done. But our findings show that’s not true,” lead study author Juhua Luo, PhD, an associate professor of Epidemiology and Biostatistics at the Indiana University School of Public Health, said in a statement. “It’s never too late, and even moderate weight loss can make a big difference when it comes to cancer risk.”

Compared with women who had stable weight, women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54-0.95). This correlation was strongest among obese women who intentionally lost weight (HR, 0.44; 95% CI, 0.25-0.78). Weight gain (≥10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormone therapy.

The trial evaluated over 35,000 women from the WHI Observational Study, which originally enrolled postmenopausal women between the ages of 50 and 79 and was initially designed to address major causes of morbidity and mortality in this specific patient population.

The investigators measured patients’ weight at the beginning of the study and then again 3 years later to assess changes over time. The patients who lost weight were asked via self-report at the 3-year follow-up mark whether their weight loss was intentional or unintentional. Weight change was categorized as stable (change within +/- 5%), loss (change ≥ 5%), and gain (change ≥5%).

The researchers then followed these women for an average of 11.4 years to identify those who were diagnosed with endometrial cancer (n = 566).

The results showed that, among women who lost 5% or more of their body weight after age 50, the risk of developing endometrial cancer was 29% lower, regardless of their age or how much weight they lost.

The greatest reduction of endometrial cancer risk was observed in patients who were obese and intentionally lost weight. Women who were obese and voluntarily lost 5% or more of their body weight saw a 56% reduction in their endometrial cancer risk.

Additionally, women who were overweight or obese and achieved a normal body mass index (BMI) after intentional weight loss were found to have the same risk as women who maintained a stable BMI.

Women who gained more than 10 pounds had a 26% higher risk of being diagnosed with endometrial cancer.

Given that endometrial cancer is known to be highly hormone-related, the study authors also analyzed their findings to determine the influence of hormone use. However, they found no significant difference in risk between women who used hormone therapy and those who did not.

“There have been more than a thousand studies linking obesity to an increased risk of endometrial and other cancers, but almost none that look at the relationship between weight loss and cancer risk,” Jennifer Ligibel, MD, ASCO Expert in Cancer Prevention, said in a statement. “This study tells us that weight loss, even later in life, is linked to a lower risk of endometrial cancer.”

These findings also support the development of weight loss programs that could potentially be embedded within a cancer prevention strategy in overweight and obese adults, explained Ligibel.

According to Karen H. Lu, MD, chair of ASCO’s Cancer Prevention Committee, this study demonstrates the potential role of weight loss in the reduction of cancer risk, as well as the notion that it is never too late to improve one’s health.

“We hope these findings will encourage individuals who may be overweight to change their behaviors to reduce the amount of food eaten and increase their physical activity,” said Lu, chair of ASCO’s Cancer Prevention Committee.

Luo J, Chlebowski RT, Hendryx M, et al. Intentional weight loss and endometrial cancer risk [published online February 6, 2017]. 

Articles

A recent study suggested that intentional weight loss could decrease the risk of endometrial cancer. 

Weight Loss Linked to Lower Endometrial Cancer Risk

The addition of hormonal therapy to radiation treatment following surgery significantly improved survival in patients with recurrent prostate cancer, according to the results of a study published in 

In the multicenter trial—which initially enrolled 760 men with biochemical recurrence after radical prostatectomy&mdash;patients were randomly assigned to treatment with bicalutamide or placebo for 2 years, along with 6.5 weeks of radiation therapy.

After a median follow-up of 13 years, the actuarial rate of overall survival (OS) at 12 years was 76.3% for patients treated with bicalutamide, compared with 71.3% for patients in the placebo group (HR, 0.77; 95% CI, 0.59-0.99; 

 = .04). The 12-year incidence of death from prostate cancer was 5.8% versus 13.4%, respectively (HR, 0.49; 95% CI, 0.32-0.74; 

 <.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group and 23.0% in the placebo group (HR, 0.63; 95% CI, 0.46-0.87; 

“Our study indicates that hormonal treatments should be incorporated into the management of men who need radiation therapy after surgery for prostate cancer," senior author Howard Sandler, MD, chair of the Department of Radiation Oncology at the Samuel Oschin Comprehensive Cancer Institute at Cedar's Sinai, said in a statement.

The double-blind, placebo-controlled trial was conducted between 1998 and 2003 and enrolled patients who had had their prostate gland removed for localized disease. Patients’ disease was originally assessed, on the basis of pathological testing, as tumor stage T2 or T3 without nodal involvement.

Eligible patients were also required to have a detectable PSA level of 0.2 to 4.0 ng/ml at least 8 weeks after surgery. Additionally, patients could not participate in the study if they had previously received chemotherapy, radiation therapy, or hormone therapy (other than preoperative short-term hormonal therapy for 2-6 months in some patients [6.4% of those enrolled]) for prostate cancer.

Salvage radiation therapy began within 12 weeks after randomization. A total dose of 64.8 Gy was administered in 36 daily fractions of 1.8 Gy at a rate of 5 sessions per week. Beginning at the initiation of radiation therapy, patients were given, on a daily schedule, either 150 mg of bicalutamide or 1 placebo tablet. Patients received their respective treatments for 24 months.

At the beginning and end of radiation therapy, the researchers evaluated patients’ clinical history, physical examination, Karnofsky performance status score, complete blood count, PSA level, serum alanine aminotransferase level, bilirubin level, and reports of any treatment-related adverse events. Subsequent follow-up evaluations were done every 3 months for 2 years, then every 6 months for 3 years, and then on a yearly basis. Bone and CT scans were performed at subsequent biochemical recurrence. Maximum androgen blockade was recommended if metastatic disease was present or if the serum PSA level rose to over 4.0 ng/ml.

The 2 groups of patients were well balanced in terms of demographic and tumor-related characteristics. The median age of patients was 65 years, and the median PSA level at study entry was 0.6 ng/ml. The median interval between surgery and the first detectable PSA level was 1.4 years, and the median interval between surgery and trial entry was 2.1 years.

The primary endpoint was the rate of OS. Prespecified secondary endpoints included disease-specific death, distant metastases, local disease progression, non—disease-specific death, any disease progression including a second biochemical recurrence, and adverse events.

A total of 21 patients treated with bicalutamide died from prostate cancer, compared with 46 patients in the placebo group. The cumulative incidence of a second biochemical recurrence at 12 years was 44.0% in the bicalutamide group, compared with 67.9% in the placebo group (HR, 0.48; 95% CI, 0.40-0.58; 

In terms of toxicity, the incidence of late adverse events associated with radiation therapy was similar between the 2 treatment arms. Gynecomastia was observed in 69.7% of the patients in the bicalutamide group, compared with 10.9% of patients in the placebo group (

"This study's findings—that adding antiandrogen therapy to the radiation typically used against recurrence reduces the incidence of metastasis, death from prostate cancer and overall deaths - will change the standard of care for patients experiencing a postoperative recurrence," study author William U. Shipley, MD, Massachusetts General Hospital Department of Radiation Oncology, said in a statement.

Shipley WU, Seiferheld W, Lukka HR, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. 

For patients with recurrent prostate cancer, adding hormonal therapy to post-surgical radiation treatment significantly improves survival, according to a recent study.

Survival Improves When ADT Added to Radiotherapy for Prostate Cancer

According to the Centers for Disease Control and Prevention (CDC), incidence rates of HPV-associated cancers continue to rise, with approximately 39,000 new HPV-associated cancers now diagnosed each year in the United States. Although HPV vaccines can prevent the majority of these cancers, vaccination rates remain low.

In response to this, The University of Texas MD Anderson Cancer Center has united with the 68 other National Cancer Institute (NCI)—designated cancer centers in issuing a joint statement that endorses the recently revised vaccination recommendations from the CDC.

The updated guidelines recommend that 11- to 12-year-old boys and girls receive 2 doses of the 9-valent HPV vaccine at least 6 months apart. Adolescents and young adults 15 and older are recommended to continue to complete the 3-dose series.

In a recent interview, Lois Ramondetta, MD, professor of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, discusses the updated recommendations and the importance of advocating for lesser-known HPV-associated cancers.

Please begin by summarizing these updated recommendations.

: The Advisory Committee on Immunization Practices voted on this in the early fall, and the Morbidity and Mortality Weekly Report came out in December, and it reported that kids who get the series started before age 15 only need 2 doses to have the same effectiveness as someone older than 15 who gets all 3 doses.

So now, the rule is that you can start as early as age 9 and, again, still as late as age 26 to have it covered by your insurance company, but if you start it even a day before your 15th birthday, you only need 2 shots, and the difference for the 2 shots is that they might be separated by a minimum of 5 months. We recommend 6 months between the first 2 shots, but you could do it even a year apart; perhaps get your first shot at age 10, and the next shot at age 11.

I am a gynecologic oncologist, and I work for MD Anderson Cancer Center, but I also work at the Harris Health System, which is a system that takes care of under-insured, sometimes uninsured, individuals, and what I see on a weekly basis are patients with advanced cervical cancer. To me, that’s my sole motivation. It’s terrible to be diagnosed with cancer, but add to that, that it could have been prevented with a shot, by screening, or Pap smears, or you could have even detected it early and then gotten rid of it, and had the patient have essentially a 100% survival rate. I’m seeing ladies come in with very large cancers, and they are losing their lives, or at least a significant quality of life. It’s appalling and sad that it’s happening everywhere in the world, but it definitely should not be happening in a developed country where we have access to everything we need to eradicate this.

On top of that, I’ve been fighting this fight for such a long time, and what we found over the last 10 years is that, the most quickly rising cancer associated with HPV is that of oropharynx cancer, and specifically, the tonsils and back of the tongue. The people who are being diagnosed are men between the ages of 55 and 65. The interesting thing about that is that these are usually insured men, and it’s not necessarily associated as much with smoking and drinking.

Fortunately, there are men out there who are raising awareness about HPV-related disease, and we’re really appreciative of that, because we haven’t been able to get the attention that we wanted. You can imagine talking to a bunch of legislators about uninsured women versus men in that specific age group; that makes their ears go up a little more.

We also know that HPV causes about 90% of anal cancers. All of these issues are things that are helping to raise awareness.

For my involvement in this, I felt like I had something to offer pediatricians and the family practice doctors by saying, “This is happening. This is not something that only happens to a particular type of person. This is something that 80% of the world will be exposed to at some point in life. We need you to pay attention, we need you to vaccinate, and it’s your job in standard of care to vaccinate and eliminate this disease.”

Do you think there’s a widespread lack of awareness about the associations between diseases like anal cancer or oropharynx cancer and HPV?

Yes, I do. I think people have only associated HPV with cervical cancer, and perhaps the marketing of the vaccine is partly to blame.

Here’s the tricky part. There’s a precancerous lesion that you can detect in both anal cancer patients and in cervical cancer patients. But at this point, we have not been able to detect precancerous lesions in the throat or tonsils. There may be 1, but it’s so far back, no one has ever found it. So most men who get diagnosed just have a lump in the neck.

Because of that precancerous lesion, they were able to show that you can use the vaccine, and it will prevent not just the infection, but the precancerous lesion too, because you have this endpoint to look for.

In terms of FDA approval, the vaccine is approved for prevention of vulvar, cervical, and anal cancer. Anal cancer is relatively rare, and in fact, we’re having a hard time finding patients with anal cancer who are willing to learn how to be better advocates. That may be because of the rarity of the disease, and maybe also the stigma. Think about Farrah Fawcett; she never told anybody about her anal cancer, and now the Farrah Fawcett Foundation is really involved.

So we have this approval, but we don’t have it for oropharynx cancer, and that might be part of why it doesn’t have as much awareness.

People think, “Well, only girls need to be vaccinated, because it’s all about cervical cancer.” What they need to know is that, by 2020, we expect more cancers in men related to HPV than women. It’s everybody’s problem, it’s a human condition, it’s something we pass to each other, and it’s 8 out of 10 people. It’s not about risky behavior; it’s the same behavior that causes pregnancy. It’s just part of intimacy, and that intimacy could be intercourse, but in many cases, it’s oral sex, or sometimes, sadly, many younger girls experiment with anal sex, because there’s that belief that a person is still a virgin even after that type of intercourse.

It’s in the mouth, too; depending on the type of kissing, you could potentially contract the infection in that way. We have the opportunity to prevent all of this, and it’s simply inexcusable that we haven’t eradicated it yet.

How are major cancer centers helping to raise awareness about research findings and best practices in this space?

The CDC and NCI offered a grant to NCI-designated cancer centers to do an environmental scan in their area of facilitators and barriers related to vaccination, and that really got a lot of people motivated. In fact, 18 institutions were given the grant, but there were so many more centers that wanted to be involved. Then this ongoing conversation started, and they ended up having the first summit at Moffitt Cancer Center, where we got together to talk about how we would all be doing this. Then the second one was held at MD Anderson Cancer Center in November 2015, and we presented the results of our scan, and we talked about what we were doing locally. We also talked about what opportunities we had to make a statement, and that’s where the first statement came from.

The third meeting was at The Ohio State University. From there, we said, “Let’s talk about what each center can do locally, not just make a national statement. How can they partner with their state immunization partnership and their state health department?” We’ve been given a bunch of suggestions on how people can do that. And that’s where we are now; the fourth summit is scheduled for South Carolina in May.

This has really motivated a lot of people. For us, when we did our environmental scan of MD Anderson and saw what was happening here, we asked, “Are we even vaccinating our own kids?” We realized we’re not doing it anymore as a community than anyone else in society overall. So we’ve done this kind of 1 year of a large campaign to raise awareness.

We also asked people, “Why aren’t you vaccinating?” Convenience factors were definitely part of it. In May of last year, we started an employee vaccination clinic, and we’ve never really done this before, but now, on the second Saturday of every month, we have a clinic at MD Anderson in the morning for employees under the age of 26, or employees’ children. It was really easy because we all accept our employee health insurance. We have had anywhere from 15 to 25 people come once a month, we’re tracking them, putting their information into the state immunization registry, and we’re doing this educational campaign. If we’re going to go out into the community to talk about this, we need to be spokespeople.

Looking ahead, what progress do you hope we’ve made in terms of awareness and getting more people vaccinated?

I think it’s going to be a very exciting 5 to 10 years. Within that time, we’ll definitely see a decrease in cervical cancers, because it takes about 10 years to get a diagnosis once you’re infected.

It’ll be awhile, decades still, before we see a decrease in anal cancer, mostly because it takes to age 65 for the average age of those patients, and probably another decade or so for seeing a decrease in the oropharynx cancer rate.

We’ll also learn how to detect oropharynx cancers better. There are a number of studies looking at ways to look for HPV type 16 in the mouth, and these are being done at many centers. MD Anderson has 1 study called the HOUSTON study, which will look at HPV in the mouth as well as serial scans, so that will be exciting.

I also think we’re going to see so much less dysplasia, because we’ve already seen a 65% decrease in the incidence of HPV infections in the age group that is being vaccinated, even though our vaccination rate is still pretty low. For completing the series of 3 doses, our rates were 42% last year, which is pretty pathetic. We’re somewhere in the 50% range for girls getting 2 shots, and around 29% for boys getting all 3 shots.

In the next decade, we’ll also be moving toward more HPV DNA testing as a primary way to test for cervical cancer. Overall, we’re just going to learn so many other things about it. Because so many people have the infection, we’ll learn which people are at higher risk for developing cancer. I think it’s a really exciting time.

MD Anderson and nation’s cancer centers jointly endorse updated HPV vaccine recommendations [news release]. Houston, TX: University of Texas MD Anderson Cancer Center; January 11, 2017. https://www.eurekalert.org/pub_releases/2017-01/uotm-maa_1011017.php. Accessed January 24, 2017.

Gynecologic oncology and reproductive medicine expert discusses the new HPV vaccine recommendations and the importance of awareness for all HPV-caused cancers.

Updated HPV Vaccinations Recommendations Endorsed

A watch-and-wait approach is emerging as a potential treatment strategy for patients with rectal cancer, according to the results of real-world data from a large observational study. These findings will be presented at the upcoming 2017 Gastrointestinal Cancers Symposium in San Francisco, CA.

After a median follow-up of 2.6 years, 25% of patients underwent delayed surgery due to a diagnosis of regrowth of their cancer. Distant metastases occurred in 7% of patients. The 3-year survival rate was 91% among all patients, and 87% among patients who experienced local cancer recurrence.

“Despite seeing excellent outcomes in our study, we know the decision to undergo surgery is personal for every patient,” said Maxime van der Valk, MD, one of the study coordinators of the International Watch and Wait Database Consortium (IWWD) and Leiden University Medical Center in Leiden, Netherlands. “When faced with the risk of permanent colostomy, some patients will prefer to avoid surgery, while others won’t want to deal with the uncertainty of their cancer potentially recurring.”

In August 2016, the database included 775 patients from 11 countries and 35 participating institutions. According to the study authors, this represents the largest series of patients with rectal cancer for whom surgery was omitted after treatment with chemotherapy and radiation therapy. Ninety percent of all patients were included in the study because of a clinical complete response (n = 679). All other reasons for a watch-and-wait approach were excluded from the present analyses.

The imaging modalities used to evaluate patients’ responses following induction therapy were variable. In 90% of cases, induction treatment consisted of chemoradiotherapy.

The median follow-up time was 2.6 years (range 0-24 years), and local regrowth occurred in 25% of all patients (n = 167). Eighty-four percent of local regrowth cases occurred in the first 2 years of follow-up.

At the time of follow-up, 25% of patients had undergone delayed surgery after a diagnosis of a cancer regrowth. Distant metastases occurred in 7% of patients. The 3-year survival rate was 91% among all patients, and 87% for patients who experienced local recurrence. These findings are consistent with historic data from patients with rectal cancer who undergo surgery.

Outcomes for patients with rectal cancer have generally improved over the last decade, with improvements in surgical techniques, the introduction of perioperative chemotherapy and radiotherapy, and improved diagnostics, says van der Valk.

However, she says, surgery in this setting still bears considerable consequences, including colostomy, sexual and urinary dysfunction, and surgical complications.

The IWWD Consortium was established in 2014 by clinical experts in the field. This international collaborative platform aims to provide evidence on safety, risks, and benefits for patients.

According to the study abstract, the current data demonstrate major, worldwide differences in the type and dose of induction therapy, as well as imaging strategies used to assess response after chemoradiotherapy.

At the present time, watch-and-wait is not a standard of care for patients with rectal cancer in any country. It is currently estimated that this approach is used in the treatment of fewer than 5% of all patients. In most countries, patients with stage II-IV rectal cancer typically receive chemotherapy and/or radiation therapy before moving on to surgery. Approximately 20% of patients see their tumors disappear completely after chemotherapy and/or radiation. However, it is not standard to re-asses or “restage” the tumor to see if surgery is still required.

Further data collection on this watch-and-wait strategy for patients with rectal cancer is warranted in order to expand knowledge on the safety of omitting surgery.

“Some people with rectal cancer undergo surgery after chemoradiation therapy, even though it may not be necessary,” said van der Valk. “From the data we have now, it seems that watch-and-wait may be safe in selected patients with rectal cancer, but it is too soon to say whether this approach should be routinely offered.”

 van der Valk M. The international watch & wait database (IWWD) for rectal cancer: an update. Abstract presented at: 2017 Gastrointestinal Cancers Symposium; January 19-21, 2016; San Francisco, CA. Abstract 521.

For patients with rectal cancer, the "watch-and-wait" approach of avoiding surgery after induction therapy is emerging as a treatment option.

Omitting Surgery Post-Treatment May Be Viable Option for Patients with Rectal Cancer

Induction chemotherapy (IC) followed by reduced-dose radiation and weekly cetuximab demonstrated improved swallowing and nutritional status as well as an excellent complete clinical response (cCR) for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), according to the results of a phase II study published in the 

Fifty-six patients (70%) achieved a primary-site cCR to IC, and 51 patients continued to cetuximab with 54 Gy of intensity-modulated radiation therapy (IMRT). After a median follow-up of 35.4 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 80% and 94%, respectively, for patients with P = .011) or had impaired nutrition (10% vs 44%; 

“We found there are some patients who have very high cure rates with reduced doses of radiation,” Barbara Burtness, MD, professor of Medicine (Medical Oncology), Yale Cancer Center, disease research team leader for the Head and Neck Cancers Program at Smilow Cancer Hospital, and the chair of the ECOG-ACRIN head and neck committee, said in a statement. “Radiation dose reduction resulted in significantly improved swallowing and nutritional status,” added Burtness.

This phase II single-arm study enrolled patients at 16 ECOG-ACRIN sites between March 2010 and October 2011. In order to be eligible for the trial, patients had to have newly diagnosed resectable, stage III/IV OPSCC positive for p16 immunohistochemistry (IHC) and/or HPV16 in situ hybridization as determined by a central laboratory.

On day 1, eligible patients were administered IC with cisplatin at 75 mg/m

. On days 1, 8, and 15, patients received paclitaxel at 90 mg/m

. Patients received cetuximab at 400 mg/m

 on day of cycle 1, followed by cetuximab at 250 mg/m

 weekly. These cycles were repeated every 21 days for 3 total cycles.

Within 2 weeks of completing IC, clinical response at the primary and involved nodal sites was determined by a complete head and neck examination, with mandatory fiberoptic nasopharyngolaryngoscopy, as well as CT or MRI.

Primary-site cCR was defined as a complete disappearance of the primary lesion on manual and endoscopic inspection. Nodal cCR was defined as complete resolution of palpable adenopathy.

The radiation dose to the oropharynx was determined by the primary site clinical response, and the nodal clinical response determined the radiation dose to involved nodes.

Patients with primary-site cCR to IC received 54 Gy in 27 fractions (IMRT) to the primary site. Those with less than cCR, on the other hand, were scheduled to receive 69.3 Gy in 33 fractions.

Involved nodes with cCR to IC received 54 Gy in 27 fractions to nodes, while those with less than cCR received 69.3 Gy in 33 fractions. A 1-cm margin was required around the involved nodes to minimize the dose administered to the oropharynx.

The uninvolved cervical nodes received 51.3 Gy in 27 fractions (1.9 Gy per fraction) to the clavicles bilaterally.

Both of these patient cohorts received weekly cetuximab to the end of radiation therapy.

Eight weeks after completion of chemoradiation, treatment response was evaluated by the radiographic method used at baseline. Patients were evaluated every 6 months for 2 years.

Late effects of treatment of lower versus standard-dose IMRT on patient-reported outcomes were measured at baseline, 12, and 24 months posttreatment using the Vanderbilt Head and Neck Symptom Survey version 2 (VHNSSv2).

This study was designed to estimate the 2-year PFS rate for patients with HPV-associated OPSCC who achieved a primary-site cCR following IC and reduced-dose radiation treatment. Secondary endpoints in the trial included safety and toxicity of the treatment, 2-year OS, and clinical and radiologic responses at the primary and nodal sites after IC and after overall treatment.

Overall, 90 patients were enrolled in the study, though 9 patients were ineligible due to out-of-window baseline scans, no measurable disease, cardiac history, and individual withdrawal from the treatment. The median age was 57 years (range, 35-73), and the majority of patients had stage T1-3 (89% of 80 eligible patients), N0-N2b (69% of eligible patients) OPSCC. Moreover, the majority were not current smokers (84%). Ninety-six percent of patients were positive for 

Seventy-seven of 80 eligible patients (96.2%) received all 3 cycles of IC. Three eligible patients received only 1 cycle due to a grade 4 cetuximab infusion reaction, grade 3 infection, and an unrelated surgical procedure, respectively. Cisplatin dose was reduced for 14 patients who experienced grade 3 or 4 hematologic toxicity, neuropathy, or tinnitus. Carboplatin was substituted in 2 patients who had grade 3 neuropathy. Eighteen patients received a modified dose of cetuximab during IC due to grade 3 or 4 acneiform rash, mucositis, or hypomagnesemia.

For patients with HPV-related oropharyngeal squamous cell carcinoma, induction chemotherapy plus reduced-dose radiation and weekly cetuximab brought improvements for swallowing and nutritional status along with complete clinical responses.

Complete Responses With Reduced-Dose Radiation in HPV-Linked Oropharynx Cancers

Patients with endometrial cancer who receive surgery in the first 2 weeks after diagnosis have worse survival outcomes, according to a study recently reported in the 

American Journal of Obstetrics and Gynecology

Moreover, an extended delay in surgical treatment was also identified to be a risk factor for mortality in low-risk endometrial cancers and was likely associated with poor access to specialty care.

“We suspect that physicians diagnosing endometrial cancer may believe, not unreasonably, that the best thing they can do for those patients is to operate as soon as possible, because if they wait too long the cancer could progress, resulting in a worse outcome,” senior author David I. Shalowitz, MD, said in a press release.

“But, the results of our study suggest that presurgical care and referring patients to a gynecologic oncologist may be more important,” added Shalowitz, who is a fellow in Gynecologic Oncology at the Perelman School of Medicine at the University of Pennsylvania.

The authors of the study suggested that the target interval between diagnosis and surgical treatment of endometrial cancers is ≤8 weeks, though they also stressed that both referral to a surgeon and preoperative optimization should be prioritized over expedited surgery.

The results of the study demonstrated that patients with low-risk cancers had a median survival time of 47.6 months (interquartile range [IQR], 25.8-73.6). The 5-year crude survival was highest when surgery was performed 3 weeks after diagnosis, and survival declined thereafter.

Patients who received surgical treatment during the first and second weeks following diagnosis (11.7%) had a higher risk of death (HR, 1.9; 95% CI, 1.7-2.1) compared with patients who underwent surgery in the third week after diagnosis (HR, 1.1; 95% CI, 1.1-1.2). Even after the researchers adjusted for age, stage, race, year of diagnosis, and additional clinical and health system characteristics, early surgery in the first and second weeks after diagnosis was still independently associated with a higher risk of death.

When surgery was performed 8 weeks postdiagnosis, the mortality risk was significantly higher than baseline and worsened as the interval between surgery and diagnosis increased.

For patients with high-risk cancers, the median survival time was 38.6 months (IQR, 18.9-67.1). As with patients with low-risk endometrial cancers, the 5-year crude survival was highest, again, when patients underwent surgery in the third week after diagnosis. Survival outcomes continued to decline thereafter.

High-risk patients who had surgery during the first and second weeks after cancer diagnosis (15.9%) had a hazard ratio for death of 2.1 (95% CI, 1.9-2.2). Surgery during this interval remained independently associated with death after the study authors adjusted for age, stage, race, year of diagnosis, and additional clinical and health system characteristics.

Surgery after the third week postdiagnosis was not correlated with a statistically significant increase in the adjusted risk of mortality, with the exception of an isolated increase seen in the nineteenth week after diagnosis.

The National Cancer Database provided cases of endometrial cancer between 2003 and 2012 for this study. Low-risk (grade 1 and grade 2 endometrioid histologies) and high-risk (grade 3 endometrioid and all other epithelial histologies) tumors were analyzed separately. The researchers limited the overall analysis to only cases for which there were data that surgery was the only modality pursued, or occurred before any hormonal, radiation, or chemotherapy treatments.

Given the results showing increased mortality risk accompanying surgery given in the first 2 weeks postdiagnosis, the investigators compared clinical and process-based factors for patients who had surgery in that short time period with patients who underwent surgery 3 and 4 weeks after diagnosis.

Patients with low-risk cancers who received surgical treatment in the first week after diagnosis were more likely to be very young or very elderly (<45 years or >85 years), Black, uninsured or with Medicaid insurance, have advanced stage disease, and undergo both diagnosis and treatment at the reporting Commission on Cancer (CoC)&shy;—accredited hospital. Plus, these patients were less likely to be treated at high-volume hospitals or be treated with lymphadenectomy.

Patients with high-risk endometrial cancers who had surgery in the first week after diagnosis were more likely to be elderly (>85), Black, uninsured or with Medicaid insurance, have advanced stage disease, and receive both diagnosis and treatment at the reporting CoC institution. Similar to the low-risk patients, they were also less likely to be treated at high-volume hospitals or undergo lymphadenectomy.

A recent study shows that expedited surgery for patients with endometrial cancer is linked to an increased risk of mortality.

Early Surgery in Endometrial Cancer Linked to Worse Survival Outcomes

An association was found between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk, according to the results of a recent study led by The Ohio State University Comprehensive Cancer Center &shy;— Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC &shy;– James) and published in the 

Compared with NSAID nonusers, NSAID use was associated with a 66% (HR, 1.66; 95% CI, 1.21-2.30) increased risk of endometrial carcinoma&shy;—specific mortality among patients diagnosed with type I tumors. This increased risk held true for both former and current users of NSAIDs, with the strongest association found among women who formerly used NSAIDs for 10 or more years (HR, 2.23; 95% CI, 1.19-4.18; 

 = .01). There was no clear association found between the use of NSAIDs and endometrial carcinoma&shy;—specific mortality among women with type II tumors.

"There is increasing evidence that chronic inflammation is involved in endometrial cancer and progression and recent data suggests that inhibition of inflammation through NSAID use plays a role," Theodore Brasky, PhD, co-lead author of the study and a cancer epidemiologist with the OSUCCC &shy;— James, said in a press release.

Brasky was surprised by these findings, given that they contrast the results of previous studies that suggest NSAIDs can be used to reduce inflammation and reduce the risk of developing or dying from certain cancers, such as colorectal cancer.

The authors of the study evaluated 4374 patients with endometrial carcinoma from the NRG Oncology/Gynecology Oncology Group 210 Study (GOG-210 Study). These patients had completed a presurgical questionnaire that assessed their history of prediagnostic NSAID use as well as endometrial cancer risk factors. Of 6124 women enrolled, 5492 (89.7%) completed the questionnaires. Medical records and cancer registries provided the researchers with patient information on recurrences, vital status, and causes of death.

Endometrial tumors were characterized as low-grade (grades 1 and 2) endometrioid carcinoma (n = 2657), high-grade (grade 3) endometrioid carcinoma (n = 582), serous carcinoma (n = 663), carcinosarcoma (n = 309), or clear cell carcinoma (n = 163). The researchers further classified low- and high-grade tumors as type I (n = 3239) and serous, clear cell, and carcinosarcomas as type II (n = 1135).

Of the 4374 patients enrolled in the GOG-210 Study, the median follow-up was 60 months after diagnosis. Five hundred fifty carcinoma-specific deaths and 737 recurrences were recorded in total.

The presurgical questionnaire included an assessment of patients’ “regular” use, which the researchers defined as 1 or more NSAID per week for 1 or more years (or more than 50 pills during any 1-year period) of aspirin, nonaspirin NSAIDs (including ibuprofen, naproxen, indomethacin, piroxicam, and sulindac), and cyclooxygenase-2 (COX-2) inhibitors.

For each NSAID type, information was also collected on duration of regular use (<1, 1-4.99, 5-9.99, and ≥10 years) and recency of regular use (former or current) relative to the date that patients completed the questionnaire. Combination exposure variables represented recency and duration based on cross-tabulations. A summary variable, referred to as “any NSAIDs,” represented patients who claimed to be regular users of aspirin, nonaspirin NSAIDs, or COX-2 inhibitors.

According to the results of this study, NSAID use was not clearly associated with any tumor characteristic, including stage, histology, myometrial invasion, lymph node involvement, peritoneal cytology, or peritoneal biopsy result.

The researchers specifically looked at the relationship between NSAID use and endometrial carcinoma&shy;—specific mortality stratified by cancer subtypes (types I and II), given the strong association between subtype and prognosis. Relative to nonuse, any use of these anti-inflammatory drugs was associated with a 66% increased risk of endometrial carcinoma&shy;–specific mortality among women with type I tumors. The risk was similar for both former and current NSAIDs users and was found to be statistically significant with 10 or more years of use. There was no association identified between NSAID use and endometrial carcinoma-specific mortality for women diagnosed with type II tumors.

However, women who formerly used NSAIDs for 10 or more years saw an approximate doubling of increased risk (HR,1.92; 95% CI, 1.20-3.08; 

 = .004) of endometrial carcinoma&shy;—specific mortality.

When the authors of the study stratified the cancers by individual histologies, they found an association between NSAID use and higher endometrial carcinoma&shy;—specific mortality for patients diagnosed with low-grade (HR, 2.18; 95% CI, 1.33-3.58) and high-grade endometrioid tumors (HR, 1.65; 95% CI, 1.03-2.62), as well as carcinosarcomas (HR, 1.54; 95% CI, 1.00-2.38). These associations were more pronounced in former and current users, but they only increased with longer duration of use for carcinosarcomas. Among patients with serous or clear cell histologies, there were no associations between NSAID use and mortality.

On the other hand, unlike mortality, any NSAID use was not associated with recurrence from type I endometrial carcinoma (HR, 1.16; 95% CI, 0.92-1.47).

When recurrence models were stratified by individual tumor histologies, any NSAID use was associated with a 54% (HR, 1.54; 95% CI, 1.03- 2.32) increased risk of recurrence among women with high-grade endometrioid tumors. A statistically nonsignificant 47% (HR, 1.47; 95% CI, 0.97-2.23) increased risk of recurrence was found among patients with carcinosarcomas. For each of these correlations, neither was strengthened by an increased duration of NSAID use.

"This study identifies a clear association that merits additional research to help us fully understand the biologic mechanisms behind this phenomenon,” said Brasky.

David Cohn, MD, gynecologic oncology division director at the OSUCCC &shy;— James and co-author of the study, said it is important to remember that these types of patients are more likely to die of cardiovascular disease than their actual cancer. Thus, women who take NSAIDs to reduce their risk of heart attack should continue to do so.

“While these data are interesting, there is not yet enough data to make a public recommendation for or against taking NSAIDS to reduce the risk of cancer-related death,” he said in a statement.

Brasky TM, Felix AS, Cohn DE, et al. Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence [published online December 16, 2016]. 

A recent study links NSAID use to an increased risk of endometrial carcinoma&shy;–specific mortality.

NSAID Use Linked to Higher Risk of Endometrial Cancer-Related Death

Patients with non—small cell lung cancer (NSCLC) treated in the pembrolizumab (Keytruda) arm of the KEYNOTE-024 trial experienced improved quality of life (QOL) compared with those treated with standard chemotherapy, according to new data from an exploratory analysis of the trial presented at the IASLC 17th World Conference on Lung Cancer in Vienna, Austria.

This prespecified exploratory patient-reported outcomes (PROs) analysis sought to determine if KEYNOTE-24’s positive results would translate into significant improvements in QOL for this patient population, an important metric in anticancer therapy as it relates to treatment in the first-line setting.

“Pembrolizumab was associated with a clinically meaningful improvement in healthcare QOL and in the time to deterioration for cough, dyspnea, and chest pain, compared with platinum-based chemotherapy,” Julie Brahmer, MD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, said in a statement.

In the KEYNOTE-024 trial, single-agent pembrolizumab reduced the risk of death by 40% and improved progression-free survival (PFS) by 4.3 months compared with doublet chemotherapy for untreated patients with advanced NSCLC who had PD-L1 expression on ≥50% of cells. These results have been hailed as practice-changing, and they have since led to the FDA approval of pembrolizumab as a frontline treatment for these patients with PD-L1 tumor expression based on an FDA-approved test, who do not harbor 

In the KEYNOTE-024 study, 305 patients were randomized to a treatment regimen of either pembrolizumab (200 mg every 3 weeks), or investigator’s choice of platinum-doublet chemotherapy, which most commonly included carboplatin plus pemetrexed. Forty-six patients in the chemotherapy arm went on to receive maintenance therapy with pemetrexed, and an additional 66 patients (43.7%) crossed over to the pembrolizumab arm following progression.

The PRO endpoints of the exploratory analysis included change from baseline to week 15 using the QLQ-C30 global health status/QOL score, as well as time to deterioration with the QLQ-LC13 composite score of cough, chest pain, and dyspnea.

PROs were analyzed for all patients who received the study treatment and completed 

1 PRO instrument (n = 299). Across all treatment arms, PRO compliance was >90% at baseline and approximately 80% at week 15.

The proportion of improved global health status/QOL score at week 15, defined as a 10-point or greater change from baseline, was 40% for patients treated with pembrolizumab and 26.5% for patients treated with chemotherapy.

In the pembrolizumab treatment arm of the study, fewer patients experienced deterioration in the QLQ-LC13 composite of cough, dyspnea, and chest pain (30% vs 39%). Plus, the time to deterioration was prolonged with the PD-1 inhibitor. Treatment-related adverse events were less frequent in patients treated with pembrolizumab.

“Combined with the superior PFS and overall survival rate of patients on pembrolizumab and manageable safety profile, these data suggest pembrolizumab may be a new standard of care for first-line treatment of PD-L1—expressing advanced NSCLC,” said Brahmer.

 Brahmer JR, Rodriguez-Abreu D, Robinson AG, et al. Health-related quality of life for pembrolizumab vs chemotherapy in advanced NSCLC with PD-L1 TPS 

50%: Data from KEYNOTE-024. Presented at: IASLC 17th World Conference on Lung Cancer; December 4-7, 2016; Vienna, Austria.

Pembrolizumab linked to improved quality of life for patients with non-small cell lung cancer (NSCLC), according to data from KEYNOTE-024 trial.

Health-Related Quality of Life Better With Frontline Pembrolizumab in NSCLC

For patients with renal cell carcinoma (RCC), having a high body mass index (BMI) could indicate an improved survival rate. While evidence shows that obesity is a risk factor for clear cell RCC, a new report shows that a high BMI is a prognostic factor for improved survival in patients with metastatic RCC who have received targeted therapy.

The authors of the study, which was published in the 

, investigated both the clinical and biologic effects of BMI on treatment outcomes in 2 distinct cohorts of patients with metastatic RCC. A high BMI was defined as >25 kg/m

The first cohort comprised 1975 patients with metastatic RCC from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), which is a consecutive patient series from institutions in North America, Europe, and Asia. The patients had received targeted therapies, such as VEGF/VEGFR and mTOR inhibitors.

In the IMDC cohort, the median overall survival (OS) was 25.6 months (95% CI, 23.2-28.6) for patients with a high BMI compared with 17.1 months (95% CI, 15.5-18.5) for patients with a low BMI (adjusted HR, 0.84; 95% CI, 0.73-0.95). The association found between BMI and OS was present in the intermediate and poor risk groups (HR, 0.73 and 0.80, respectively), but not in the favorable group (HR, 1.05).

Patients with high BMI had improved time to treatment failure compared with low BMI in both first- and second-line therapy after adjustment for the IMDC prognostic factors.

Similar results were found in the second cohort, which was an external validation cohort. The validation cohort was a pooled analysis of prospective data from 4657 patients with metastatic RCC treated in phase II and III trials sponsored by Pfizer involving sunitinib (Sutent), temsirolimus (Torisel), and axitinib (Inlyta).

The adjusted hazard ratio for OS in this cohort was 0.83 in favor of the group of patients with a high BMI. The overall response rate was 25.3% in patients with a high BMI compared with 17.6% in patients with a low BMI (adjusted odds ratio, 1.53). Both the overweight (BMI, 25 to <30 kg/m

) groups tended to have prolonged progression-free survival and OS in the first- and second line settings.

In order to investigate the underlying biologic differences associated with different BMI groups, the authors focused on the role of the fatty acid synthase (FASN) pathway in patients with metastatic RCC. FASN expression is considered a metabolic oncogene in multiple tumor models, and it has previously been reported to be associated with poor prognosis in several tumor types, including RCC.

The researchers used available genomic data of mRNA expression from patients who were part of the Kidney Renal Clear Cell Carcinoma clinical TCGA consortium. A total of 61 patients with metastatic RCC were identified in this cohort. Patients in the high BMI group (n = 39) had lower FASN expression compared with the low BMI group (n = 22; 

 = .03), and high FASN was associated with worse OS (median, 15 vs 36.8 months for high FASN vs low FASN, respectively).

In a final analysis, the researchers used samples from the IMDC cohort to assess the relationship between BMI and FASN IHC expression. Tissue mircroarrays were used from 146 patients with metastatic RCC who had received targeted therapy.

FASN staining positivity, which was recorded in 45 (31%) cases overall, was more frequently detected in poor (11/23; 48%) and intermediate (20/59; 34%) risk groups compared with the favorable risk group (5/30; 17%; 

-trend = .02). When stratified by FASN IHC expression, OS was 27.5 months (95% CI, 19.3-36.7) in FASN-negative patients versus 14.5 months (95% CI, 10.4-20.5) in FASN-positive patients (HR, 1.71; 95% CI, 1.17-2.51; P = .005). However, the authors noted that, “The adjusted HR of FASN was reduced to 1.28 (95% CI, 0.84-1.95) in the multivariable model, with adjustment of IMDC risk group and BMI.”

In contrast, when adjusted for IMDC risk groups and FASN, BMI remained associated with OS (adjusted HR, 0.44; 95% CI, 0.29-0.66), and this correlation was observed in both FASN-negative (HR, 0.39; 95% CI, 0.24-0.64) and FASN-positive groups (HR, 0.55; 95% CI, 0.27-1.13; 

Several hypotheses have been proposed to explain the association between a high BMI and improved survival outcomes. Nishihara et al

 suggested that the correlation can be reconciled by disease heterogeneity, such that the longer survival among obese patients compared with normal-weight patients is due to a less aggressive disease subtype. The current findings support this theory because FASN gene expression was found to be downregulated in obese patients compared with patients who had a normal BMI. Moreover, higher FASN expression was associated with worse survival.

“This data seems more specific to RCC, where obesity seems to portend a favorable prognosis in metastatic disease,” Toni K. Choueiri, MD, senior author of the study and clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, said in an interview with 

The results of the study pave the way for further exploration of the biology of this association as well as therapeutic approaches that may come of it.

“We plan to take our findings back to the laboratory to discover any therapeutic implications around the FASN pathway,” said Choueiri.

Albiges L, Hakimi AA, Xie W, et al. Body mass index and metastatic renal cell carcinoma: clinical and biological correlations [published online September 6, 2016]. 

Nishihara R, VanderWeele TJ, Shibuya K, et al. Molecular pathological epidemiology gives clues to paradoxical findings. 

Despite obesity as a risk factor for clear cell RCC, a high BMI is a prognostic factor for improved survival in patients with metastatic RCC.

High BMI Indicates Improved Overall Survival in Patients with RCC

While primary cytoreductive surgery followed by chemotherapy is the standard of care for newly diagnosed women with advanced ovarian cancer, newly issued practice guidelines suggest that some patients may benefit more from first-line neoadjuvant chemotherapy (NACT)  and interval cytoreduction.

The clinical practice guideline was developed by experts with the American Society of Clinical Oncology (ASCO) and the Society of Gynecologic Oncology (SGO) and published August 8 in the 

“This guideline is a big step forward in one of the most contentious areas within gynecologic oncology,” said Alexi A. Wright, MD, co-chair and ASCO’s representative on the Expert Panel that worked on developing the guideline.

The evidence supporting these recommendations comes from four phase III clinical trials, which found that for women with stage IIIC or IV epithelial ovarian cancer, NACT and interval cytoreduction were preferable to adjuvant chemotherapy and primary cytoreduction with respect to overall and progression-free survival.

However, it is important to note that women with suspected stage IIIC or IV invasive epithelial ovarian cancer should seek evaluation by a gynecologic oncologist before beginning either type of therapy, according to one of the new guideline recommendations. Such an evaluation should include a CT of the abdomen and pelvis with oral and intravenous contrast and chest imaging (CT preferred) to determine the extent of disease, as well as whether the patient is a candidate to undergo primary cytoreductive surgery (PCS) with acceptable risks and associated morbidity.

Other tools may be used to assess patients as well, such as laparoscopic evaluation or additional radiographic imaging (FDG-PET scan or diffusion-weighted MRI). However, the use of these methods has been found to be inferior to CT findings at this time.

For women who are assessed by a gynecologic oncologist and are determined to be a fit for PCS, with potentially resectable disease, either PCS or NACT can be offered as treatment. With respect to progression-free and overall survival, as well as perioperative morbidity and mortality, NACT has been found to be generally noninferior to PCS. Neoadjuvant chemotherapy is associated with less peri- and postoperative morbidity and mortality and shorter hospitalizations. Primary cytoreductive surgery, on the other hand, may offer superior survival results in patients with newly diagnosed stage IIIC or IV epithelial ovarian cancer.

The benefits of these respective therapies come from the results of 4 randomized clinical trials comparing NACT and interval cytoreduction with primary cytoreduction and chemotherapy among women with advanced ovarian cancer.

Allie Strickler