ASCO 2018: Many women with early-stage breast cancer can safely skip chemotherapy

A majority of women with early-stage breast cancer will not require to undergo chemotherapy says the results of very important clinical trial presented Sunday, June 3, 2018, at the American Society of Clinical Oncology (ASCO) annual clinical meeting in Chicago, Illinois and is also being published simultaneously in the New England Journal of Medicine.

This federally funded phase III randomized clinical trial is a game changer for most women diagnosed with early-stage breast cancer who are hormone receptor-positive, HER2-negative, axillary node-negative and who received a mid-range score on the Oncotype DX gene test.

"Half of all breast cancers are hormone receptor-positive, HER2-negative, and axillary node-negative," noted study author Dr. Joseph Sparano, MD, Associate Director for Clinical Research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and Vice-Chair of the ECOG-ACRIN Cancer Research Group.

"Our study shows that chemotherapy may be avoided in about 70 percent of these women when its use is guided by the test, thus limiting chemotherapy to the 30 percent who we can predict will benefit from it," Sparano said in a news release from the American Society of Clinical Oncology (ASCO).

The Oncotype DX test looks at 21 separate genes in breast tumor cells samples and quantifies the individual risk of recurrence and likelihood of benefits from post-surgical chemotherapy. The test results give patients a "score" based on a continuous scale from 0-100.

Onco-surgeons are using this score since long to guide them about decisions on post-surgical chemotherapy. A woman with a low score (1-10) will only receive hormonal therapy while if she scores high (26-100), she receives additional chemotherapy also to prevent recurrence.

It was not clear how to proceed with treatment decisions for women who received the scores in mid-range 11-25. “The trial was designed to address this question, and provides a very definitive answer,” added Sparano.

The Trial Assigning IndividuaLized Options for TReatment (TAILORx) (ClinicalTrials.gov: NCT00310180) recruited 10,273 women 18-75 years of age diagnosed with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer.

Of those, 6,711 had a mid-range Oncotype DX test score of 11-25 and were randomly assigned to receive hormone therapy alone or hormone therapy and chemotherapy.

After a median follow-up of 7.5 years, it was seen that the rates of overall survival, disease-free survival, or cancer spread beyond the breast was comparable for both the groups.

Adding chemotherapy only benefited a small subgroup of women who scored between 16-25 on the Oncotype DX test and were younger than 50 years.

Based on the results, the researchers concluded:

Chemotherapy can be safely omitted in women with this type of breast cancer who have an Oncotype score under 26 and are older than 50 years (85 % of women with breast cancer in this age group).

Chemotherapy can also be omitted in women who are younger than 50 and have an Oncotype score less than 16 (about 40% of women with breast cancer in this age group).

This study received funding primarily from the National Cancer Institute, part of the National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and the U.S. Postal Service Breast Cancer Stamp. The ECOG-ACRIN Cancer Research Group designed and conducted the study.

ASCO press release

Full-Text NEJM

Ob/Gyn Updated Facebook page

Using scalp cooling systems prevent hair loss by 50% in patients receiving cancer chemotherapy.

Dignicaps

Use of cooling caps or cooling systems during cancer chemotherapy for early stage breast cancer reduces the hair loss by almost 50% according to two studies published simultaneously on February 14 in Journal of American Medical Association.

The most dreaded complication of cancer chemotherapy is hair loss, nearly 50% of patients report it to be the most traumatic aspect of chemotherapy. Additionally, 8% of patients who could have benefitted from it refuse to undergo chemotherapy fearing the hair loss.

Although Cooling caps and have been in market since some time, but their use was not backed by scientific studies. The two recent RCTs use different systems for cooling the scalp, but both show positive results.

The investigators explain that cooling results in constriction of scalp blood vessels, reducing the amount of chemotherapeutics delivered to the hair follicles thereby reducing hair loss.

  

The article by Nangia et al. in this issue of JAMA report the result of SCALP trial, a multicenter, randomized trial testing 182 women with breast cancer receiving chemotherapy with a taxane, anthracycline, or both. This trial used Orbis Paxman Hair Loss Prevention System (Paxman Coolers Ltd), which has yet to receive FDA approval in the United States.[i]

Paxman.com

The Paxman system comprises of a small compact mobile refrigeration system connected to two lightweight silicone caps, the inner one is made of silicone and outer one is of neoprene.

The patient’s scalp is lowered in temperature to approximately 18°C by circulating a special coolant throughout the cap at -4°C.

Scalp cooling was carried out for 30 minutes each before and during therapy and 90 minutes after the therapy is over for each session of chemotherapy infusion.

The study results showed variable results depending upon type of agent used and clinical expertise of the treating physician. Hair retention rate was 16% inpatient anthracycline-based regimen vs. 59% in those on taxane-based regimen.

The second study by Dr.Hope S. Rugo and colleagues used the DigniCap, approved by FDA  for use in the United States since 2015.The study used Dean scale to assess hair loss and none of the patient in the study group received anthracyclines.[ii]

Nearly 66%of study participants experience 50% less hair loss assessed at 4 weeks after therapy as compared to 0% in control group.

“Despite difference in study designs, inclusion criteria and type of device, the results of these two studies are reassuringly similar: scalp cooling was associated with prevention of significance hair loss in approximately 50% of patients,” says Dawn L. Hershman, MD, MS, from the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, in an accompanying editorial.[iii]

"Identifying interventions, such as scalp cooling for the prevention of chemotherapy-induced alopecia, that reduce or eliminate treatment-associated toxic effects will help ease the distress associated with chemotherapy and may, as a result, improve outcomes for patients with breast cancer," Dr Hershman concludes.

Fear that scalp metastasis will not be eradicated because of decline in drug delivery due to cooling is the number one reason that scalp cooling devices have not been very popular in the United States. In this study a median follow up of 29.5 months in patients in the scalp cooling group has not demonstrated any evidence of metastasis.

Link to Nangia study abstract.

Link to Rugo study abstract

Link to Hershman editorial extract.

Two nonprofits organization in US offer help to women and men undergoing chemotherapy access and use scalp-cooling technology to help keep their hair.  They are The Rapunzel Project and The Hair to Stay Foundation. Visit the site by clicking the link for more information.

                                             DigniCap - What is Scalp Cooling

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[i] http://jamanetwork.com/journals/jama/article-abstract/2601500

[ii] http://jamanetwork.com/journals/jama/article-abstract/2601503

[iii] http://jamanetwork.com/journals/jama/article-abstract/2601483

ASCO issues evidence based, global guidelines for managing invasive cervical cancer.

The American Society of Clinical Oncology (ASCO) has issued recommendation on managing invasive cervical cancer.  There exist wide disparities in screening, diagnosing and treatment of patient diagnosed with invasive cervical cancer across the globe. Economic disparity and lack of resources make it impossible to adopt the same guidelines universally. 

ASCO has first time published ‘resource stratified’ guidelines that are tailored according to the resources available in a specific region.

The guidelines were published online before print on May 25, 2016, in Journal of Global Oncology.

According to WHO statistics, an estimated one million-plus women worldwide are currently living with cervical cancer of which about 84 per cent occur in less developed countries.

Dr. Linus Chuang, MD, MS, professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York City, who is cochair of the ASCO expert panel that developed the guideline said "In those regions, access to pathology services, skilled surgeons, radiation machines, brachytherapy, chemotherapy, and palliative care may all be constrained." 

Dr. Jonathan S. Berek, MD, MMS, professor and chair of obstetrics, gynecology, and gynecologic oncology at the Stanford University School of Medicine in California, and who is also cochair of the ASCO expert panel opined that At least two-thirds of the women who die from cervical cancer have not had regular screening, "If we improved screening and HPV vaccination around the world, we might be able to substantially decrease the mortality from cervical cancer." 

ASCO called upon a multidisciplinary, multinational panel of cancer specialist, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to develop   guidelines that encompasses resource tiered settings.  A systemic review of literature from the year 1966 to 2015 could not yield sufficiently strong evidence to develop tailored guidelines across the different region globally, so a formal strategy of developing consensus based guidelines was adopted.

Five sets of guidelines from different bodies and societies were reviewed in current context and recommendations were formed into 4 tier that is basic, limited, enhanced, and maximal. For surgery, chemotherapy and radiotherapy treatment combinations and modalities available were formed according to the 4 tier.

1. Surgery: In basic tier Simple (extrafascial) hysterectomy or more extensive hysterectomy can be performed while in maximal  tier facilities Radical hysterectomy, radical trachelectomy, pelvic and paraaortic LN sampling, sentinel node biopsy, and pelvic exenteration; radiation therapy, chemotherapy, interventional radiology, palliative care service, and bevacizumab are all available.
2. Chemotherapy:  In basic tier availability of chemotherapy drugs were unpredictable, while in maximal capacity Chemotherapy available; bevacizumab is also available.
3. Radiotherapy: In basic tier no radiation therapy available while RT including external beam and brachytherapy and interventional radiology available in maximal capacity.

The societies were the National Comprehensive Cancer Network (NCCN) in the United States, and the World Health Organization (WHO), Cancer Care Ontario (CCO) in Canada, the European Society of Medical Oncology (ESMO), the Japan Society of Gynecologic Oncology (JSGO).

Workup, Optimal therapy, follow up and post treatment surveillance and palliative care were earmarked for each of these tiers and stage of cancer.

ASCO emphasized that health care providers and health care administrators should be guided by the recommendations from the highest stratum of resource available to provide women with the best evidence based treatment modality and palliative care.

Some of the key recommendations in treatment for invasive cervical cancer are:

• In Basic setting where radio therapy is not available, extrafascial hysterectomy, either alone or after chemotherapy, can be an option for women with stage IA1 to IVA cervical cancer.
•  In Enhanced and Maximal settings, concurrent radiotherapy and chemotherapy is the standard of care for women with stage IB to IVA disease.
• Adding  Low dose chemotherapy to Radiotherapy is  ideal, but if chemotherapy is not available the radiotherapy should not be delayed for it.
• In limited resource settings where brachytherapy is not available, extrafascial hysterectomy or its modification in patients who still have residual tumor of 2-3 months after concurrent radio and chemotherapy.
• Those patients with stage IV or recurrent cervical cancer in basic settings can be treated with single agent chemotherapy using carboplatin or cisplatin.
• In patients who have disseminated disease and cannot be cured should be given palliative radiotherapy to relieve pain and bleeding.
• In areas with very poor resources, multiple short courses of radiotherapy can be used for retreatment of recurrent or residual diseases.
• In settings where good follow up care can be provided, cone biopsy in basic resources settings and cone biopsy and lymphadenectomy in limited resource setting is the treatment of choice for 1A2 disease. 
• For patients in enhanced and maximal settings, to preserve the fertility in reproductive age group of women radical trachelectomy is recommended for those with stage IB1 disease with tumor size up to 2 cm.
• ASCO also noted that the current guidelines are intended to complement the existing guidelines and not necessary replace it.
• ASCO also provided future directions and stressed the need for prospective comparative research. Radical versus simple hysterectomy (the feasibility and safety of performing cone biopsy or simple hysterectomy) is an active area of investigation in limited resource settings, with stage IA2 versus 1B1 disease.

References:

http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/cervical-cancer-statistics

http://www.who.int/reproductivehealth/topics/cancers/en/

http://www.asco.org/sites/new-www.asco.org/files/content-files/practice-and-guidelines/documents/2016-RS-Cervical-Cancer-Treatment-Summary-Table.pdf

http://jgo.ascopubs.org/content/early/2016/05/21/JGO.2016.003954.full