Highlights from the 2015 European Cancer Congress

TON November 2015 Vol 8 No 6 - Conference Correspondent

In This Article

 

The 2015 European Cancer Congress (ECC 2015) was held in Vienna, Austria, from September 25 to 29. The congress was jointly sponsored by the European CanCer Organisation (ECCO) and the European Society for Medical Oncology (ESMO). This year’s congress represents the last time these 2 organizations will jointly sponsor a biennial meeting. In the future, ESMO and ECCO will hold separate meetings.

Below is a summary of some of the highlights from ECC 2015. These studies were selected because they are relevant for nurses, nurse practitioners, physician assistants, and other advanced practitioners who work with patients with cancer.


Ovarian Suppression During Chemotherapy

Temporary ovarian suppression with a luteinizing hormone-releasing hormone agonist (LHRHa) during chemotherapy for breast cancer preserves ovarian function and prevents premature menopause in women of childbearing age, according to a meta-analysis presented at ECC 2015, and published simultaneously online in Annals of Oncology.1,2 Use of ovarian suppression during chemotherapy also led to a higher number of patients achieving pregnancy posttreatment.

“Chemotherapy can damage the ovaries and push young women into menopause. They may experience infertility, sleep disturbance, sexual dysfunction, and osteoporosis. It is psychologically distressing, harmful to health, and affects treatment decisions of many young women,” said Matteo Lambertini, MD, a medical oncologist at the IRCCS Azienda Ospedaliera Universitaria San Martino IST, Genova, Italy.3

Guidelines regarding ovarian suppression in this setting are inconsistent, he explained. The 2013 guidelines from the American Society of Clinical Oncology state that ovarian suppression is experimental, and should not be used outside of clinical trials.

Recently the POEMS study showed an increase in the number of pregnancies in women with hormone receptor–negative breast cancer who received ovarian suppression with an LHRHa during chemotherapy. This led the 2015 St. Gallen International Expert Consensus panel guidelines and the National Comprehensive Cancer Network guidelines to acknowledge the role of LHRHa in preventing chemotherapy-induced ovarian failure, but only in hormone receptor–negative breast cancer, Dr Lambertini said.

“Both POEMS and the PROMISE-GIM6 study show improvement in preservation of ovarian function and fertility in women with breast cancer who receive hormonal treatment in addition to chemotherapy,” he noted. PROMISE-GIM6 included mostly women with hormone receptor–positive breast cancer. That study has been submitted for publication.

The pooled meta-analysis he presented was based on 12 randomized trials (including POEMS and PROMISE-GIM6), with a total of 1231 patients with breast cancer receiving chemotherapy, with or without LHRHa. Rates of premature ovarian failure (POF) were reduced by 64% in patients who received LHRHa. The studies used different definitions of POF, however, and results varied widely.

Dr Lambertini and his coauthors then restricted the analysis to studies with data on women whose menstrual cycles had not resumed within 1 year after chemotherapy, which is in line with the World Health Organization’s definition of menopause. Among 8 relevant trials, the overall reduction in POF remained striking in the group of women treated with an LHRHa, with a reduction of 45%.

In this analysis, “there was close agreement in results from all studies,” Dr Lambertini stated.

Although LHRHa was originally used to preserve ovarian function, in 5 studies that reported on pregnancies after cancer treatments, there were 33 patients with pregnancies among those treated with hormonal therapy, and 19 pregnancies among women who did not get ovarian suppression, reflecting an 83% increase in the likelihood of becoming pregnant. The rate of pregnancies was consistent across the 5 studies.

“We believe there is now sufficient evidence to suggest that the administration of LHRHa could be considered a potential standard strategy to preserve ovarian function, and might also play a role in increasing the likelihood of pregnancy after chemotherapy. …This strategy could be useful and safe not only in women with hormone receptor-negative breast cancer, but also in those with hormone receptor-positive tumors, who account for two-thirds of new cases of breast cancer in young women,” Dr Lambertini explained.

“I hope this is deemed a valid option to be offered to patients to preserve ovarian function and fertility,” he added.

References
1. Lambertini M, Ceppi M, Poggio F, et al. Ovarian suppression with luteinizing hormone-releasing agonists during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients: a systematic review and meta-analysis of randomized studies. Presented at: European Cancer Congress 2015; September 25-29, 2015; Vienna, Austria.
2. Lambertini M, Ceppi M, Poggio F, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann Oncol. 2015 Sep 7. Epub ahead of print.
3. European Society for Medical Oncology. Young women undergoing chemotherapy for breast cancer may be more likely to remain fertile if they also receive hormonal treatment [press release]. Vienna, Austria: European Society for Medical Oncology; September 28, 2015. www.esmo.org/Conferences/European-Cancer-
Congress-2015/News/Hormonal-Therapy-Could-Pre vent-Ovarian-Failure-and-Preserve-Fertility-in-Wom en-with-Breast-Cancer. Accessed October 6, 2015.


Timing of Sentinel Node Biopsy

Patients with melanoma can be reassured that the time interval between primary surgical excision and sentinel node (SN) biopsy does not affect survival. Thus, patients do not have to immediately undergo SNbiopsy. These were the results of a retrospective, multicenter cohort study presented as a late-breaker in the Presidential Session at ECC 2015.

In SN-negative and SN-positive patients, melanoma-specific survival was not significantly different for any excision–SNbiopsy time interval cutoff from 1 to 8 weeks.

“Our results show that there is no scientific rationale to advocate a strict time limit between primary excision and sentinel node biopsy,” said Charlotte Oude Ophuis, MD, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands.

“Subanalyses in matched cohorts from the 4 centers with data on both SN-positive and SN-negative patients (n = 2848) confirmed our finding that the time interval until SNB [sentinal node biopsy] had no significant impact on melanoma-specific survival and disease-free survival,” she said.

Most international guidelines recommend re-excision plus SNbiopsy as soon as possible after primary excision, she explained. Some even add a time limit as to when SNbiopsy should be performed; that is, <6 weeks. There are no data to support this recommendation, which imply that there would be a detrimental effect if the time limit were exceeded.

The study analyzed data from 998 SN-positive melanoma patients from 9 different centers, and 2886 SN-negative melanoma patients from 4 different centers, diagnosed between 1993 and 2012, and with known primary excision dates. Compared with SN-negative patients, those who were SN-positive had tumors that were thicker (median Breslow thickness, 3.0 mm vs 1.7 mm), and more likely to be ulcerated (44% vs 25%).

Median time interval between primary excision and biopsy was similar in the 2 groups: 46 days in SN-positive patients, and 42 days in SN-negative patients.

No significant associations were found between tumor or baseline characteristics and time interval in SN-positive patients. Among SN-negative patients, older age and thinner tumors were associated with a shorter time interval until SNbiopsy.

Reference
Oude Ophuis C, Verhoef C, Rutkowski P, et al. The interval between primary melanoma excision and sentinel node biopsy (SNB) does not affect survival; regardless of SNB status – an EORTC Melanoma Group study. Presented at: European Cancer Congress 2015; September 25-29, 2015; Vienna, Austria.


Support for Patients with Head and Neck Cancer

A new study provides insight as to when patients with head and neck cancer (HNC) might need the most support. Although human papillomavirus (HPV)-positive HNC is associated with longer survival and better outcomes, these patients require more support during the acute treatment phase, whereas those who have HPV-negative HNC will probably require more long-term support.

“The drop in quality of life [QOL] in p16-positive patients is quite dramatic during the acute treatment phase. These patients may require additional support during this period. Conversely, p16-negative patients have lower [QOL] in the longer term, and may need more long-term support,” said lead author Hisham Mehanna, MD, Institute of Head and Neck Studies and Education, University of Birmingham, United Kingdom.1

The study was conducted by a team from various centers across the United Kingdom who investigated outcomes and QOL in 564 patients with HNC enrolled in the phase 3, PET-NECK trial, which was conducted to compare PET-CT–guided active surveillance with planned neck dissection following primary radical chemoradiotherapy. Of 446 patients tested, 75% tested positive for the p16 protein, an important gene product involved in the pathogenesis of HNC.2

P16-positive patients had better baseline health scores compared with p16-negative patients, but their mean change in score (−33.9) was significantly greater than that of p16-negative patients (−18.4) during the acute phase of treatment. Nevertheless, p16-positive patients recovered to a better level of global health by 2 years after treatment.

Dr Mehanna acknowledged that it is not clear why patients with HPV-positive disease responded differently. He said it is possible that the effects of chemoradiotherapy on HPV-positive tumors may result in a different pattern of cytokine release, causing more pain or other symptoms in the acute period.

“We know that patients with HPV-positive tumors tend to be younger nonsmokers from better socioeconomic backgrounds, while those with HPV-negative disease tend to be older, with a history of heavy smoking and alcohol use, and are often from lower socioeconomic backgrounds,” he suggested. “This may mean that those who develop HPV-positive [HNC] have different personality or lifestyle traits, and hence, different coping mechanisms.”

References
1. Mehanna H, Wong WL, McConkey CC, et al. Differences in the quality of life (QoL) and functional outcomes of treatment between HPV associated (HPV+) and HPV- patients receiving primary chemoradiotherapy in PET-NECK - a multi-centre randomized phase III controlled trial (RCT) comparing PETCT guided active surveillance with planned neck dissection (ND) for locally advanced (N2/N3) nodal metastases (LANM) in patients with head and neck squamous cell cancer (HNC) treated with primary radical chemoradiotherapy (CRT). Presented at: European Cancer Congress 2015; September 25-29, 2015; Vienna, Austria.
2. Stephen JK, Divine G, Chen KM, et al. Significance of p16 in site-specific HPV positive and HPV negative head and neck squamous cell carcinoma. Cancer Clin Oncol. 2013;2:51-61.


Late Toxicity in Head and Neck Cancer

Late toxicities in head and neck squamous-cell carcinoma (HNSCC) treated with concurrent chemoradiation were common and had functional consequences. These late effects are usually underreported in the literature, with no uniformity, said T. Giollo
Rivelli, MD, Brazil.

“Close follow-up of these patients is essential. It is important to diagnose and to treat to improve their quality of life, to avoid life-threatening conditions, and to prevent social reclusion,” he told listeners.

At a supportive care session during ECC 2015, Dr Rivelli reviewed late toxicity associated with chemoradiation. “Cisplatin-based chemotherapy as adjuvant or definitive therapy is usually given concurrently in [patients with] HNSCC with locally advanced disease, and results in a gain of 6.5% in 5-year overall survival,” he explained.

The study was conducted to identify the frequency of later toxicity in patients with HNSCC treated with cisplatin-based chemoradiation, with no evidence of disease for ≥2 years after treatment.

From 2014 to 2015, after signing informed consent, 76 patients answered a questionnaire about their perception of late toxicities. These patients were also evaluated using the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Schema for toxicities of the mucous membrane, skin, subcutaneous tissue, salivary glands, larynx, and esophagus. They also underwent fiberoptic nasopharyngolaryngoscopies (NPLs) and upper gastrointestinal endoscopies. Median follow-up was 40 months after chemoradiation.

The majority of patients were male, with a median age of 59 years. The majority had a history of cigarette smoking and alcohol use. Most of the survivors had Eastern Cooperative Oncology Group performance status scores of 0 to 1.

Of the 76 patients in the study, 45% had oropharyngeal cancers, 22% had laryngeal cancers, 18% had cancers of the oral cavity, 8% of the hypopharynx, and 7% of the nasopharynx; 71% were node-positive.

According to responses to the questionnaire, patients reported the following symptoms: xerostomia (84%), dysphagia (72%), hypothyroidism (71%), voice changes (71%), sticky saliva (71%), hearing loss (58%), tracheostomy (22%), pneumonia (13%), feeding tube dependence (4%), and fistulae (4%).

Looking at late radiation morbidity scores on the RTOG/EORTC schema, most patients had some degree of toxicity. The majority had mild toxicities, with 56% at grade 1, and about 15% at grade 2. No grade 4 toxicities were reported. Frequency of grade ≥1 toxicity was as follows: salivary gland (84%), subcutaneous tissue (83%), mucous membrane and skin (74% each), esophagus (72%), and larynx (66%).

Stenosis of the pharynx or esophagus was diagnosed in 3 of 41 patients. Most common findings in 61 patients who underwent NPLs were edema in 74%, fibrosis in 44%, radiation-induced mucositis in 43%, and changes in bolus propulsion in 15%; laryngeal penetration was diagnosed in 6 of 51 patients, and aspiration in 3 patients.

Reference
Rivelli TG, Simão EF, Mak MP, et al. Long term toxicities after cisplatin-based concurrent chemoradiation in head & neck squamous cell carcinoma (HNSCC) disease-free patients: a cross-sectional study. Presented at: European Cancer Congress 2015; September 25-29, 2015; Vienna, Austria.


Visualization and Relaxation Techniques Reduce Anxiety in Patients Receiving Chemotherapy

Diagnosis and treatment of cancer commonly causes anxiety and depression for patients and their families. It would seem intuitive that visualization and relaxation techniques could help allay anxiety and depression. A randomized controlled trial provides hard evidence that addressing anxiety and depression with these techniques is helpful.

“A diagnosis of cancer and its treatment brings distressed emotional states to patients and families, leading to symptoms such as sleep difficulties, fatigue, and pain. These changes in behavior can affect treatment by impairing cognition, weakening motivation, decreasing coping abilities, and compromising quality of life,” said Andreas Charalambous, MD, Cyprus University of Technology, Nursing Department, School of Health Sciences, Limassol.

In this study, patients undergoing treatment for breast or prostate cancer (N = 212) were randomized to 3 weeks of standard care (ie, referral to a psychologist; control group), or relaxation and visualization exercises (intervention group); their levels of anxiety and depression were then assessed with the SAS and BECK-II questionnaires, respectively. In addition, saliva cortisol and saliva amylase levels were measured to assess the effects of the in­terventions, since stress activates the hypothalamic-pituitary-adrenal axis, increasing peripheral cortisol known to result in depressed mood, he explained.

Relaxation exercises involved breathing and muscle tensing and releasing, as well as guided imagery sessions that were 15 minutes long. The intervention group received 4 weekly supervised sessions of relaxation exercises and guided imagery, and also performed daily unsupervised sessions.

The mean anxiety score for the intervention group gradually decreased over 3 weeks, whereas the mean anxiety score increased for controls. The same pattern was seen in mean depression scores.

“The change from baseline to the third week for both measures was highly significant,” Dr Charalambous told the audience.

The next step was to assess cortisol levels pre- and postintervention. “We know guided imagery and relaxation are good for patients, but is the body really relaxed? The cortisol levels reflect that,” he said.

Cortisol levels gradually decreased up to week 3 in the intervention group, whereas the opposite occurred in controls. The same was true for amylase levels.

“These findings suggest that a more comprehensive management program is needed to combat anxiety and depression in cancer patients. Because anxiety and depression are not life-threatening, they have not received the attention they deserve,” Dr Charalambous noted.

“Fifty-five percent of patients will develop some sort of depression, and 65% [of patients] will experience anxiety. This is an accident waiting to happen. We have to be prepared to intervene before that accident occurs,” he stated.

Reference
Charalambous A, Giannakopoulou M, Bozas E, Paikousis L. Visualization and relaxation as anxiety reducing techniques in breast and prostate cancer patients undergoing chemotherapy: findings from a randomized controlled trial. Presented at: European Cancer Congress 2015; September 25-29, 2015; Vienna, Austria.

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Last modified: November 20, 2015