When Care Comes at a Cost: Preventing and Managing Symptoms for Optimal Patient Outcomes

Friday, May 18 • 9:45–11 am

Note one action you’ll take after attending this session: ______

1. The Effect of Aromatherapy and Foot 3. Implementing Preventative Low Level Laser Therapy in Reflexology on Pain and Anxiety During Hematopoietic Stem Cell Transplant Patients to Prevent Brachytherapy for Cervical Cancer Oral Mucositis: Follow-Up of Patient Outcomes Catherine Hill, BSN, RN, OCN Ashley Layton, BSN, RN, OCN The Arthur G. James Cancer Hospital and the Richard L. University of Pittsburgh Medical Center, Shadyside Hospital Solove Research Institute Pittsburgh, PA Columbus, OH 4. Abating Alopecia: Treating Hair Loss as a Chemo 2. Development of Education and Guidelines in Toxicity in Breast Cancer Patients (Male & Female) Management of Patient Care for Immune Kaddie Lopez, BSN, RN, OCN, PHN Effector Cell Administration—Chimeric Antigen City of Hope Receptor (CAR) T-Cell Therapy Duarte, CA Margaret Blaney, RN, BSN University of Rochester Medical Center Rochester, NY

Oncology Nursing Society 43nd Annual Congress Clinical Practice May 17–20, 2018 • Washington, DC 1 ONS 43rd Annual Congress

When Care Comes at a Cost: Preventing and Managing Symptoms for Optimal Patient Outcomes

The Effect of Aromatherapy and Foot Reflexology on Pain and Anxiety During Brachytherapy for Cervical Cancer

Catherine Hill BSN, RN, OCN Clinic RN, James Radiation Oncology Clinic

Catherine Hill • No disclosures

Clinical Practice (Hill) 1 ONS 43rd Annual Congress

Brachytherapy and Cervical Cancer

. The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation: external beam radiation therapy with concurrent chemotherapy followed by brachytherapy. . Gynecological brachytherapy is the delivery of high dose radiation internally through placing applicators and then a radioactive source inside the uterus and/or vagina. . Brachytherapy allows the administration of high doses of radiation to the primary tumor while sparing dose to the normal tissues at risk, resulting in improved local control and survival compared to those who do not receive brachytherapy.

Research Protocol Objective:

Does the addition of aromatherapy and foot reflexology to standard care improve pain and anxiety in patients receiving brachytherapy for cervical cancer?

Brachytherapy – Ring and Tandem Applicators

Used with permission from A. Quick MD

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Brachytherapy Delivery • High Dose Radiation Remote After-loader

PAIN with Brachytherapy

PARASYMPATHETIC STIMULATION

Used with permission from the National Cancer Institute

Brachytherapy Study: 5 KEY TIME POINTS

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Brachytherapy: 5 FRACTION SCHEDULE

Brachytherapy

40%

Used with permission from MedLinePlus

Pre study - Brachytherapy Patient Database (N=49 from 2015 & 2016)

Pain and anxiety medications given in addition to anesthesia for the 1st fraction:

 Lorazepam Average Dose across  Morphine Sulfate 5 fractions  Ketorolac  Hydromorphone = 40 OME  Hydrocodone (oral morphine equivalent)  Oxycodone

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Pre study - Brachytherapy Patient Database (N=49 from 2015 & 2016)

OMEs 50 44 43 40 40 40 31 30 20 OMEs 10 0 ANESTHESIA FX #1 FX #2 FX#3 FX #4 FX#5 OMEs Across Fractions

Complementary and Alternative Medicine: Aromatherapy and Reflexology

. Aromatherapy – use of essential oils to improve physical and mental health and quality of life . Lemon, Lavender, Peppermint . Reflexology – manual technique based on the zone theory that points on feet correspond to part of the body; also thought to relieve pain by transmitting afferent impulses to block pain transmission

Used with permission from K. Thompson MS, RN, PMHCNS-BC

Brachytherapy Study

Clinical Practice (Hill) 5 ONS 43rd Annual Congress

Tools

• Pre Anxiety assessment tool

• Pain & Anxiety on study tool

Tools

. Post study Final Evaluation of Aromatherapy/Reflexology

Study Database: N=10 as of January 2018

OMEs Across Fractions

Clinical Practice (Hill) 6 ONS 43rd Annual Congress

Brachytherapy Study Results to date; N=10

3.06 AVE PAIN Aroma/Reflex 5.25 Control

0246810

Brachytherapy Study Results to date; N=10

31 AVE ANXIETY Aroma/Reflex

45 Control

0 1020304050

Brachytherapy Study Results to date; N=10

79 AVE OME Aroma/Reflex 98 Control

0 20406080100120

Clinical Practice (Hill) 7 ONS 43rd Annual Congress

Brachytherapy Study: Final Evaluation N=4

Aromatherapy EXPERIENCE2 REDUCED PAIN Reflexology REDUCED ANXIETY

0246810

Aromatherapy/Foot Reflexology Patient Comments: . “I just couldn’t believe how much the treatments helped relieve my pain and anxiety---And my relaxation lasted all day….even after going home!”

. “I couldn’t say that I didn’t mind coming in for treatment because of the aromatherapy and reflexology, but it certainly made it easier knowing I had that to look forward to!”

. “It was just wonderful! Better than I imagined!”

Key Takeaways • Addition of aromatherapy and reflexology does improve pain and anxiety in patients receiving brachytherapy for treatment of cervical cancer. • Use of non-pharmacological interventions is relatively inexpensive to supply and train staff to provide this service for patients. • Addition of non-pharmacological interventions should be considered for other treatment modalities due to the potential reduction of administration of narcotics and benzodiazepines.

Clinical Practice (Hill) 8 ONS 43rd Annual Congress

References

Amsbaugh, A.K., Amsbaugh, M.J., El-Ghamry, M.N., Berhake, B.M. (2016). Optimal epidural analgesia for patients diagnosed as having gynecologic cancer undergoing interstitial brachytherapy. Journal of Clinical Anesthesia, 35, 509-515. Buckle, J. (2007). Literature review: Should nursing take aromatherapy more seriously? British Journal of Nursing, 16(2), 116-120. Gill, B.S., Lin, J.F., Krivak, T.C., Sukumvanich, P., Laskey, R.A., Ross, M.S., Lesnock, J.L., Beriwal, S. (2014). National cancer data base analysis of radiation therapy consolidation modality for cervical cancer: The impact of new technological advancements. International Journal of Radiation Oncology Biological Physics, 90(5), 1083-1090. Hines, S., Steels, E., Chang, A., Gibbons, K. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database of Systematic Reviews. 2012, Issue 4. Art. No.: CD007598. http://dx.doi.org/10.1002/14651858.CD007598.pub2. Hodge, N.S., McCarthy, M.S., & Pierce, R.M. (2014). A prospective randomized study of the effectiveness of aromatherapy for relief of postoperative nausea and vomiting. Journal of Peri-Anesthesia Nursing, 29(1), 5-11. Kirchheiner, K., Czajka-Pepl, A., Ponocny-Seliger, E., Scharbert, G., Wetzel, L., Nout, R.A., Sturdza, A., Dimopoulos, J.C., Dorr, W., & Potter, R. (2014). Posttraumatic stress disorder after high-dose-rate brachytherapy for cervical cancer with 2 fractions in 1 application under spinal/epidural anesthesia: Incidence and risk factors. International Journal of Radiation Oncology, 89(2), 260-267. Kwekkeboom, K.L., Dendaas, N.R., Straub, M., & Bradley, K.A. (2009). Patterns of pain and distress during high-dose-rate intracavity brachytherapy for cervical cancer. Journal of Supportive Oncology, 7(3), 108-114. Neron, S., Perez, S., Benc, R., Bellman, A., Rosberger, Z., & Vuong, T. (2014). The experience of pain and anxiety in rectal cancer patients during high-dose-rate brachytherapy. Current Oncology, 21(1), 89-95. Perez, S., Neron, S., Benc, R., Rosberger, Z, & Vuong, T. (2016). The meaning and experience of patients undergoing rectal high-dose-rate brachytherapy. Cancer Nursing, 39(1), 42-50. Tsay, S.L., Chen, H.L., Chen, S.C., Lin, H.R., & Lin, K.C. (2008). Effects of reflexotherapy on acute postoperative pain and anxiety among patients with digestive cancer. Cancer Nursing, 31(2), 109-115. Weibe, E., Surry, K., Derrah, L., Murray, T., Hammond, A., Yaremko, B., & D’Souza, D. (2011). Pain and symptom assessment during multiple fractions of gynecologic high-dose rate brachythearpy. Brachytherapy, 10, 352-356.

Clinical Practice (Hill) 9 ONS 43rd Annual Congress

Development of Education and Guidelines in Management of Patient Care for Immune Effector Cell Administration- Chimeric Antigen Receptor (CAR) T-cell Therapy

Meg Blaney, RN, Rhona Henry, RN, Brittany Estlinbaum, RN, Anna Morrison, RN

Wilmot Cancer Institute, University of Rochester Medical Center

Disclosures • No disclosures

Clinical Practice (Blaney) 1 ONS 43rd Annual Congress

What is CAR T‐cell Therapy: “A Living Drug”

• Immune Effector Cell therapy uses the power of a patient’s immune system to combat disease.

• T cells are collected ad genetically engineered to recognize and attack tumors by producing special receptors on their surface called chimeric antigen receptors (CARs).

• Engineered CAR T cells are grown in the lab and then infused into the patient.

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Objectives 1. Develop infrastructure to administer CAR T‐cell therapy (Nursing, Program Leadership, Providers, Finance, Pharmacy’ Stem Cell Processing Facility, Apheresis Collection Facility, IT Security, URMC Privacy Officer) 2. Establish standards and quality guidelines 3. Create guidelines for management of toxicities 4. Provide education to all appropriate team members

Experience in B‐Cell Malignancies • NCI experience* – B-Lineage ALL • AE: Cytokine Release Syndrome Gr III-IV (29%), Neurotoxicity 52%, Hypotension 56%, Anemia 50%, Thrombocytopenia 44% • ORR 71% with CR rate of 57% – Diffuse Large B-Cell Lymphoma (DLBCL) • AE: Any AE 95%, any SAE 58% • ORR 68% with CR rate of 41% • WCI experience – Clinical trials for: DLBCL, ALL, Mantle Cell Lymphoma (MCL), Follicular Lymphoma

*Lee DW, Gardner R, Porter DL, et al. How I treat: current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 May 29. pii: blood-2014-05-552729.

Program Development • To administer cellular therapy products: – Abide by all federal and state regulations – Develop practice standards to support therapy • BMT program had in place: – Adherence to federal, state, FACT regulations – High quality care practices – Developed care standards – Staff educated in cellular therapy administration

Clinical Practice (Blaney) 3 ONS 43rd Annual Congress

Developing Standards of Care • Collaboration between BMT and Lymphoma teams – BMT Standards in place for cryopreserved HCT products – Training protocols in place for BMT team – Institutional guidelines – Education for other services providing patient care events • CAR T‐cell specific standard development – Utilized references in study protocols and current BMT SOPs to develop new care standards – Developed educational materials to train all staff including: • BMT unit staff • BMT Advanced Practice Providers • BMT Attending Physicians • ICU Nursing • ICU Attending Physicians

Standards of Care • Developed standard of care for administration of product. • Based upon current standards for cryopreserved product infusion. • Validated procedure • Created checklist for administration to ensure all requirements were met

Management of Toxicities • Some adverse events (AE) similar to BMT: – Neutropenic fever, sepsis, thrombocytopenia, • Some AE very specific to CAR T‐cell Therapy: – Cytokine Release Syndrome (CRS) • Result of release of cytokines from targeted cells • Fever, hypotension, tachycardia, renal dysfunction • Onset 1‐5 days post therapy, resolution 1‐3 weeks – Neurotoxicity • Aphasia, dysphagia, somnolence, seizure, tremor • Median onset 6 days (range 2‐17 days)

Clinical Practice (Blaney) 4 ONS 43rd Annual Congress

Cytokine Release Syndrome Extensive co‐morbidities or older age? Treatment Grading assessment No/Yes

Grade 1: • Vigilant supportive care • Fever (defined as ≥ 38.3oC) N/A • Assess for infection • Constitutional symptoms • Treat fever and neutropenia if present, monitor fluid balance, antipyretics, analgesics as needed

Grade 2: • Hypotension: responds to fluids or one low dose • As above for grade 1 vasopressor No • Monitor organ function closely • Hypoxia: responds to <40% O2 • Monitor with continuous cardiac telemetry and • Organ toxicity: grade 2 pulse oximetry

Grade 2: Yes • As above for grade 2 • Hypotension: responds to fluids or one low dose • Consider tocilizumab (8mg/kg, not to exceed vasopressor 800mg) ± corticosteroids (e.g., • Hypoxia: responds to <40% O2 methylprednisolone 1mg/kg BID or • Organ toxicity: grade 2 dexamethasone 10mg q6hrs)

Grade 3: N/A • Hypotension: requires multiple vasopressors or high dose vasopressors A • Hypoxia: requires ≥ 40% O2 • Organ toxicity: grade 3 or grade 4 transaminitis

Grade 4 N/A As above for grade 2/3 • Mechanical ventilation Corticosteroids (e.g., methylprednisolone 1g/day x3, • Organ toxicity: grade 4 excluding transaminitis followed by a rapid taper consisting of 250mg BID x2 days, 125mg BID x2 days and then 60mg BID x2 days)

Staff requirements • Developed training and education requirements • Patient education standardized • Outlined requirements prior to administration of CAR T‐cell product – Availability of Tocilizumab – Yescarta REMA patient wallet card – REMS administrator

Education/Training • Education and training per BMT standards • REMS Training • SOP for – Outlined training requirements for staff – Guided patient education – Ensured critical care elements required prior to administration of therapy were met • Patient education • FACT Standards

Clinical Practice (Blaney) 5 ONS 43rd Annual Congress

Critical Documents Developed

• SOP for Eligibility Criteria • SOP for Administration of Immune Effector Cells • CAR T‐cell Infusion Checklist • SOP for Managing Toxicities and Complications of Immune Effector Cell Therapy • SOP for Staff Requirements for Immune Effector Cell Therapy Program (REMS) • Apheresis Collection Checklist for CAR T‐cell Therapy • Stem Cell Processing Facility Standards • Equipment Validation Protocol • SOP for Management of BMTU Water Bath Equipment • Water Bath Temperature Monitor • Day of Use BMTU Water Bath Cleaning Log • IEC Audit and Assessment tool and audit template • SOP for Written Agreements with Third Parties • Stem Cell Processing Facility SOPs

What we didn’t know when we started…

• How to manage equipment and equipment monitoring • Need for temperature monitoring • Purchasing a digital thermometer and having NIST certification performed prior to receipt would have saved about three weeks’ time • Agreements • REMS program requirements • Program development is a full time job • Need to make sure you have dedicated staff • Ensure that you have a program leader who is familiar with FACT and FDA standards, and who is capable of representing your program requirements to the manufacturer.

Conclusions • Having the right team members present is important (know your resources) • Have a dedicated leader familiar with regulatory and quality requirements • Education development for staff is key • Establish training guidelines • Validate

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References

• Kochenderfer JN, et al. Chemotherapy‐refractory diffuse large B‐cell lymphoma and indolent B‐cell malignancies can be effectively treated with autologous T cells expressing an anti‐CD19 chimeric antigen receptor. J Clin Oncol. 2015 Feb 20;33(6):540‐9. • Lee DW, Gardner R, Porter DL, et al. How I treat: current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 May 29. pii: blood‐2014‐05‐552729. • Neelapu SS, et al. Axicabtagene Ciloleucel CAR T‐Cell Therapy in Refractory Large B‐Cell Lymphoma. N Engl J Med. 2017 Dec 10.

Clinical Practice (Blaney) 7 ONS 43rd Annual Congress

Implementing Preventative Low Level Laser Therapy in Hematopoietic Stem Cell Transplant Patients to Prevent Oral Mucositis: Follow Up of Patient Outcomes

Ashley Layton, RN, BSN, OCN Erin Bartell, RN, BSN, CCRN, BMTCN Sharon Hanchett, BSN, MSN, OCN Annette Quinn, RN, MSN 1

Disclosure

The speakers have no financial or other conflicts of interest to report.

Background

• Oral mucositis (OM) is one of the most incapacitating side effects experienced by hematopoietic stem cell transplant (HSCT) patients.

• 97% of patients receiving busulfan experience mouth ulcers.

• The effect of preventative Low Level Laser Therapy (LLLT) was measured using a cohort of 19 patients who received busulfan.

• Impact was measured by examining each patient’s OM toxicity level, need for a patient controlled analgesic (PCA) and if additional therapy, specifically methotrexate, was held due to the severity of OM.

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Oral Mucositis (OM)

• Caused by a complex process of injury to rapidly dividing epithelial cells that line the oral cavity • Contributing risk factors: • Local tissue damage • Ex: Alcohol &/or tobacco use • Local oral environment • Ex: Poor oral hygiene • Patient’s level of myelosuppression • Based on chemotherapy type, dose & regimen • Patient’s intrinsic genetic predisposition • Ex: Poor salivary function

Sonis, 2007

Oral Mucositis (OM)

• OM has the ability to: • Modify/Delay/Suspend Treatment • Create need for opioid analgesic • Require enteral/parenteral nutrition • Increase cost of care/LOS • Impact patient survival

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Low Level Laser Therapy (LLLT)

• May 2014, MASCC/ISOO released new recommendations for the management of mucositis • LLLT recommended to prevent OM in patients receiving stem cell transplants conditioned with high dose chemotherapy & undergoing radiation for head/neck cancers

Low Level Laser Therapy (LLLT)

• Benefits of LLLT: • Reduction of pain due to increased endorphins • Reduction of inflammation via reduction in IL‐1 & C‐RP • Tissue healing as a result of increased neovascularization & macrophage activity

Quinn & Dest, 2016

LLLT at Shadyside Hospital

• Barb King, a UPMC Shadyside patient/staff member, received LLLT many times during her AML treatment

• She recognized the promise this technology held & wrote for the grant from the Shadyside Hospital Foundation that would fund our project

• The good work we are doing here today is thanks to her recognition of this technology & dedication December 14th, 2015 to patients

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Interventions

• All LLLT treatments were administered on MWFs

• If the busulfan was administered on any other day of the week, LLLT treatment was initiated the following MWF closest to the first day of busulfan administration

• LLLT was discontinued when the patient’s ANC remained ≥ 500 for 2 consecutive days

• Administered in conjunction with education on proper mouth hygiene • Normal saline swish after each meal & before bedtime • Sodium bicarbonate toothpaste • Proper mouths inspections

Purpose

To determine:

1. If preventative LLLT impacted the patient’s quality of life by preventing or eliminating severe OM while receiving a busulfan conditioning regimen

2. If the patient’s pain level was controlled to the degree of not requiring a PCA

3. If the patient continued to receive all methotrexate as ordered

Evaluation

OM Toxicity Grading Grade 1: 3 patients (16.7%) N = 18 Grade 2: 3 patients (16.7%) Grade 3: 12 patients (66.7%) Grade 4: 0 patients (0%)

Grade 1 Grade 2 Grade 3 Grade 4

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Evaluation PCA for Pain Control n = 18

Only 6 patients (33.3%) required a PCA

PCA No PCA

Analgesic Effect

Piva et al. states “LLLT has shown to be an anti‐ inflammatory alternative with effects similar to those observed in therapy with nonsteroidal anti‐ inflammatory drugs (NSAIDs), inhibiting and/or decreasing the concentration of prostaglandin ES2 (PGE2), cyclooxygenase 2 (COX2) and histamine.”

Evaluation

Dose of Methotrexate n = 16

8 patients (50%) were able to continue their conditioning treatment & received full methotrexate doses

(Note: 3 patients excluded)

Decreased Full

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Discussion

Preventative LLLT is an excellent tool used to reduce OM toxicity!

Benefits: • Allows more patients to receive their full chemotherapy regimens • Decreases the use of PCAs • Provides extraordinary patient satisfaction while improving quality of life

Discussion

Challenges: • Difficult to look at patient weights • Confusion between esophagitis & OM • Difficulty determining Toxicity Grading • Different RN to RN • Difficulty identifying thrush vs. OM

“Will I get my laser treatment “This is the best!” today?” “I couldn’t go through this without this treatment”

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Innovation

With proven efficacy, UPMC Shadyside has now expanded to treating other oncology patient populations who are at increased risk for developing OM.

Key Takeaways:

Preventative LLLT: 1. Improves patient’s quality of life by preventing or eliminating severe OM while they receive busulfan conditioning regimens during their hematopoietic stem cell transplant. 2. Can decrease a patient’s pain level to the degree that they do not require a PCA for OM during their hematopoietic stem cell transplant. 3. Can allow patients to continue to receive all methotrexate as ordered during their hematopoietic stem cell transplant.

References

• Bensinger, W., Schubert, M., Ang, K., Brizel, D., Brown, E., Eilers, J.G., Elting, L., Mittal, B.B., Schattner, M.A., Spielberger, R., Treister, N.S., Trotti, A.M. (2008). NCCN task force report: Prevention and management of mucositis in cancer care. Journal of the National Comprehensive Cancer Network 6(1). • Brunner, L. S., Suddarth, D. S., Smeltzer, S. C., & Bare, B. G. (2014). Brunner & Suddarth's textbook of medical‐surgical nursing. Philadelphia: Lippincott Williams & Wilkins. • Piva, Juliana Aparecida de Almeida Chaves, Abreu, Elizângela Márcia de Carvalho, Silva, Vanessa dos Santos, & Nicolau, Renata Amadei. (2011). Effect of low‐level laser therapy on the initial stages of tissue repair: basic principles. Anais Brasileiros de Dermatologia, 86(5), 947‐ 954. https://dx.doi.org/10.1590/S0365‐05962011000500013 • Quinn, B., Baker, D.L. (2015). Comprehensive oral care helps prevent hospital‐acquired nonventilator pneumonia. American Nurse Today 10(3). • https://www.thorlaser.com/oralmucositis/

Clinical Practice (Layton) 7 ONS 43rd Annual Congress

Abating Alopecia: Treating Hair Loss as a Chemo Toxicity in Breast Cancer Patients (Male & Female) Kaddie Lopez, BSN RN OCN PHN Clinical Nurse Manager City of Hope National Medical Center

Disclosures • None

Clinical Practice (Lopez) 1 ONS 43rd Annual Congress

Chemo-Induced Alopecia (CIA) • Caused by damage to hair follicles from certain chemotherapies • Highly publicized potential adverse effect of chemo treatment • Cosmetic Issue vs. Chemo Toxicity

Scalp Hypothermia • Treatment used to prevent CIA • Process of “cooling”/ “freezing” scalp during chemo infusion • Different companies & methods available • Cost is 100% out of pocket

Infusion Room Study

• Pre Study Analysis • Purpose • Population

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Infusion Room Study

• Implementation • Evaluation

Key Takeaways • Alopecia continues to be widely viewed in the clinical world as a cosmetic issue instead of a true chemo toxicity that can lead into significant psychosocial adverse effects. • In small study- 64% of participants lost <50% of hair with scalp cooling. Satisfaction and effect pf psychosocial status varied from person to person. • Many logistical, operational, and ethical challenges.

References

• Barbor, M MPH.(2014). The Psychological Effects of Chemotherapy-Induced Alopecia. Supportive Care, 7, No. 5. http://www.theoncologynurse.com/ton-issue- archive/2014-issues/september-october-vol-7-no-5/16240-the-psychosocial-effects- of-chemotherapy-induced-alopecia-ton • NCI- National Cancer Institute (2017). FDA Clears Wider Use of Cooling Cap to Reduce Hair Loss during Chemotherapy. https://www.cancer.gov/news- events/cancer-currents-blog/2017/fda-cooling-cap-chemotherapy

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