CommunityFeature Report Journal Club A round-up of ASCO’s 2013-2014 guideline releases, updates, and endorsements Bernard A Mason, MD

uring the past year, the American Society colon cancer treatment outside of a clinical trial of Clinical Oncology (ASCO) has pub- because of lack of evidence and the danger of false Dlished 7 special articles that create, update, positives. Likewise, the routine chest X-ray has lit- or endorse clinical practice guidelines. All 7 articles tle use when CT scans of the chest are being done are the subject of this month’s review. periodically. Routine laboratory studies other than the car- Follow-up care, surveillance, and cinoembryonic antigen (CEA) blood test, such as secondary prevention measures for CBC and liver function tests have not been rec- survivors of colorectal cancer1, 2 ommended since before 2005. Finally, the current Since 2006, ASCO has adopted a policy of endors- guidelines recommend secondary prevention eforts ing clinical practice guidelines developed by oth- such as maintaining body weight, physical activity, ers in order to increase the number of such guide- and a healthy diet, although there is little high-qual- lines available for ASCO membership. Recently, ity evidence for these behaviors. the society endorsed the guidelines for colon can- cer follow-up created by the Cancer Care Ontario Answer: d (CCO). Tese guidelines include surveillance rec- ommendations that are very similar to the 2005 Sentinel lymph node biopsy for women ASCO guidelines and the current NCCN guide- with early-stage breast cancer3,4 lines, with a few minor diferences. However, unlike Since the 2005 ASCO guidelines for sentinel node NCCN and previous ASCO guidelines, the current biopsy were published, there have been 9 random- guidelines include statements about secondary pre- ized clinical trials and 13 cohort studies pertinent to vention, written survivorship plans for the patient’s the issue of sentinel node biopsy (SLB) and axillary other providers, and the futility of surveillance tests node dissection (ALND) available for expert panel in patients who are not candidates for surgery or review. Te current version includes some changes systemic therapy due to comorbid disease. in the standard of care. A direct comparison of the 2005 and 2014 recommendations is online. Which of the following was specifcally recommended in the endorsed CCO guidelines Sentinel node biopsy should be ofered to women for the follow-up care of patients with colon with breast cancer in the following circumstances: cancer: a) Operable breast cancer and multicentric disease a) PET/CT chest, abdomen, and pelvis annually b) Large or locally advanced breast cancer b) Complete blood count (CBC) and liver function c) Pregnant women with breast cancer tests d) DCIS in women undergoing breast conservation c) Chest X-ray and radiation therapy d) Maintaining healthy body weight, physical activ- ity, and eating a healthy diet Axillary lymph node dissection should be performed in: Key points a) Women with 1-2 sentinel lymph nodes who are Te current ASCO-endorsed guidelines (as well being treated with breast conservation and whole as those of the NCCN) specifcally recommend breast radiation therapy. against the use of PET scans for surveillance after b) Women without sentinel node metastases.

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c) Women with sentinel node metastases who are being twofold increase in breast cancer recurrence which is not treated with mastectomy. improved by a boost of radiation therapy, systemic adju- d) Women with DCIS vant therapy, or clinical factors such as favorable biology. Moreover, results are not improved by re-excising for wider Key points margins compared to negative margins as defned by no According to the guidelines, women may be not be candi- ink on tumor. Tis applies to patients who are younger dates for SLB if they have DCIS and are undergoing breast than 40, those with increased intraductal component to conservation and radiation therapy, because of a lack of evi- the tumor, and those with higher grade tumors biologi- dence about its efcacy and concerns about lymphedema. cally. Implementation of these new guidelines will result in Likewise, there is insufcient evidence to justify SLB in a decrease in re-excision rates, which will improve cosmetic women with large and locally advanced invasive tumors, results, and a reduction in overall health care costs. infammatory breast cancer, and in pregnancy. However, there is moderately strong evidence to support SLB in Answer: a only women with multicentric tumors. Review of the literature and analysis has led to strong Adjuvant endocrine therapy for women with recommendations for not performing ALND in women hormone receptor–positive breast cancer8-11 with negative SLB, in those with DCIS, and even in In late May 2014, the Journal of Clinical Oncology those with 1 or 2 SLN metastases, based on recent trials. published a focused update of the previous guidelines and However, ALND is recommended in women being treated updates that had been published in 2002, 2003, 2004, and with mastectomy who had positive SLB. 2010. However, even this, the most recent guideline for adjuvant endocrine therapy of early breast cancer, is already Answers: a and c, respectively somewhat out of date because of recent data. Te early results of the SOFT/TEXT trials presented at ASCO Margins for breast-conserving surgery with 2014 and recently published, provided a new option for whole-breast irradiation in stage I and II premenopausal women – exemestane plus ovarian ablation. invasive breast cancer5-7 A multidisciplinary consensus panel review reviewed data According to the guidelines, which of the following is from 33 studies comprising 28,162 patients and analyzed not currently a recommended adjuvant hormonal the surgical margin and its relationship to the develop- therapy for a menopausal woman: ment of ipsilateral breast cancer recurrence. Te consensus a) Tamoxifen for 10 years guideline developed by the Society of Surgical Oncology b) Aromatase inhibitor for 5 years and the American Society for Radiation Oncology was c) Tamoxifen for 5 years, followed by an aromatase inhibi- endorsed by ASCO. Te results are practice changing, and tor for 5 years this new standard for the adequate margin for invasive can- d) Tamoxifen for 2-3 years, followed by an aromatase cer should reduce re-excision rates and health care costs, as inhibitor for up to 5 years for up to a total of 8 years well as improve overall cosmetic results. e) Aromatase inhibitor for 10 years

Surgical margins for the lumpectomy specimen for Key points women undergoing breast-conserving surgery with For postmenopausal women, the guideline recommenda- whole-breast radiation should be (include all that are tions have changed since the publication of the ATLAS correct): trial earlier this year. For women who received tamoxi- a) No ink on tumor fen for an initial 5-year course, a decision must be made b) 2 mm as to whether to administer another 5 years of tamoxifen c) Wider in younger women, especially under age 30 or switch the patient to an aromatase inhibitor for 5 years. d) Wider margins for extensive intraductal component to Either course of action is acceptable according to the new the cancer guidelines. For those women who had already received tamoxifen for 2-3 years, aromatase inhibitor may be given Key points for up to 5 years, for a total of up to 8 years of endocrine For women choosing breast conserving surgery with therapy. whole breast irradiation instead of modifed radical mas- Tere are insufcient data to recommend an aromatase tectomy, the surgical margin may be a determining factor inhibitor for longer than 5 years, either as initial therapy or in the risk of ipsilateral breast cancer recurrence. A posi- following tamoxifen. For patients who begin their therapy tive margin, defned as ink on tumor, is associated with a with an aromatase inhibitor, but are intolerant and cannot

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complete 5 years, tamoxifen may be given to complete a ASCO panel found no evidence for the efcacy of any total of 5 years. neuroprotective agents, although there was intriguing evi- dence for a beneft for venlafaxine from a small study, but Answer, e not enough to recommend yet. Larger trials of this agent were recommended. For treatment of existing neuropathy Screening, assessment, and management of only duloxetine could be recommended, particularly for fatigue in adult survivors of cancer12 oxaliplatin neuropathy. Calcium and magnesium infusions Most cancer patients will experience fatigue during their were thought to protect from neuropathy in early studies, treatment, and almost one-third will continue to com- but subsequent confrmatory trials were negative. Acetyl-L plain for years after treatment. For the current ASCO carnitine and lamotrigine have been found to have no ben- fatigue guideline, adaptation methodology was used to eft in phase 3 studies. adapt already existing guidelines from the pan-Canadian and NCCN guidelines for screening, assessment and care Answer: a of cancer-related fatigue plus the NCCN guidelines for survivorship. Systemic therapy for patients with advanced human epidermal growth factor receptor Which of the following does not reduce fatigue in 2-positive breast cancer14 cancer survivors? ASCO has created a new guideline for the treatment of a) Modafnil metastatic disease in the HER2-positive patient, and b) Mindfulness-based intervention includes recommendations based on data for newer agents c) Cognitive behavior therapy that have been recently approved including pertuzumab d) Maintaining physical activity and emtansine (T-DM1). New frst-, second-, and third- line recommendations are ofered, as well as guidance about Key points the use of hormone therapy in such patients. Tere are conficting reports of the usefulness of psycho- stimulants in cancer patients, with recent randomized trials Appropriate choices for the third-line treatment being more negative than positive. However, there is scant metastatic breast cancer in a woman with HER2- evidence that such drugs are useful to treat fatigue in can- positive and ER-positive disease includes all except: cer survivors. Other psychosocial interventions, including a) Emtansine (T-DM1) mindfulness-based intervention and cognitive behavioral b) Pertuzumab therapy as well as initiating and maintaining physical activ- c) Lapatinib + capecitabine ity have been proven to be useful. d) Hormonal therapy e) Chemotherapy Answer, a Key points Prevention and management of According to the guidelines, third-line therapy for patients chemotherapy-induced peripheral with HER-2 positive breast cancer includes T-DM1 or neuropathy in survivors of adult cancers13 pertuzumab for those who haven’t yet received these agents, For guideline development, 48 randomized clinical trials lapatinib plus capecitabine, lapatinib and trastuzumab, hor- published over a period of 23 years were drawn from 1,252 monal therapy with or without an HER2-targeted therapy potential citations. Each trial was assessed for study quality, if the tumor was ER positive. Chemotherapy alone without and usefulness of pharmacologic agents in prevention or HER2-targeted therapy was not recommended. treatment of chemotherapy-induced neuropathy. Answer: e

With of the following ameliorates the symptoms of References chemotherapy-induced neuropathy? 1. Meyerhardt JA, Mangu PB, Flynn PJ, et al. Follow-up care, surveil- a) Duloxitine lance, and secondary prevention measures for survivors of colorectal b) Acetyl-L-carnitine cancer: American Society of Clinical Oncology Practice Guideline Endorsement. J Clin Oncol. 2013;31:4465-4470. c) Lamotrigine 2. Desch CE, Benson AB 3rd, Somerfeld MR, et al. Colorectal cancer d) Calcium and magnesium infusions surveillance: 2005 update of an American Society of Clinical Oncol- ogy Practice Guideline. J Clin Oncol. 2005;23:8412-8519. 3. Lyman GH, Temin S, Edge SB, et al. Sentinel lymph node biopsy for Key points patients with early-stage breast cancer: American Society of Clini- After careful evaluations of the current evidence, the cal Oncology Clinical Practice Guideline Update. J Clin Oncol.

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2014;32:1365-1383. 9. Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with 4. Lyman G, Giuliano AE, Somerfeld MR, et al. American Society of ovarian suppression in premenopausal breast cancer. N Engl J Med. Oncology Guideline Recommendations for sentinel lymph node bi- 2014;371:107-118. opsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703-7720. 10. Rugo HS. Hormone therapy in premenopausal women with early- 5. Buchholz TA, Somerfeld MR, Griggs JJ, et al. Margins for breast- stage breast cancer. N Engl J Med. 2014;371:175-176. conserving surgery with whole-breast irradiation in stage I and 11. Davies C, Pan H, Godwin J, et al. Long-term efects of continuing II invasive breast cancer: American Society of Clinical Oncology adjuvant tamoxifen to 10 years versus stopping at 5 years after diag- Endorsement of the Society of Surgical Oncology/American So- nosis of oestrogen receptor-positive breast cancer: ATLAS, a ran- ciety for Radiation Oncology Consensus Guideline. J Clin Oncol. domised trial. Lancet. 2013;381:805-816. 2014;32:1502-1506. 12. Bower JE, Bak K, Berger A, et al. Screening, assessment, and man- 6. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical agement of fatigue in adult survivors of cancer: an American Society Oncology-American Society for Radiation Oncology Consensus of Clinical Oncology Clinical Practice Guideline Adaptation. J Clin Guideline on margins for breast-conserving surgery with whole- Oncol. 2014;32:1840-1850. breast irradiation in stages I and II invasive breast cancer. J Clin On- 13. Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and col. 2014;32:1507-1515. management of chemotherapy-induced peripheral neuropathy in 7. Hunt KK, Sahin AA. Too much, too little, or just right? Tumor mar- survivors of adult cancers: American Cancer Society of Clinical On- gins in women undergoing breast-conserving surgery. J Clin Oncol. cology Clinical Practice Guideline. J Clin Oncol. 2014;32:1941- 2014;32:1401-1406. 1967. 8. Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine thera- 14. Giordano SH, Temin S, Kirshner JJ, et al. Systemic therapy for pa- py with hormone receptor-positive breast cancer: American Society tients with advance human epidermal growth factor receptor 2-posi- of Clinical Oncology Clinical Practice Guideline Focused Update. J tive breast cancer: American Society of Clinical Oncology Clinical Clin Oncol. 2014;32:2255-2269. Practice Guideline. J Clin Oncol. 2014;32:2078-2099.

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