CORD-19-Sentences  

CORD-19:c738a511a9c18e7e831b40f1ec3605fe4cdeb6d1 JSONTXT 7 Projects

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TextSentencer_T1 0-345 Sentence denotes Journal Pre-proof Breast radiotherapy under COVID-19 pandemic resource constraints --approaches to defer or shorten treatment from a Comprehensive Cancer Center in the United States Breast radiotherapy under COVID-19 pandemic resource constraints --approaches to defer or shorten treatment from a Comprehensive Cancer Center in the United States
TextSentencer_T2 347-355 Sentence denotes Abstract
TextSentencer_T3 356-476 Sentence denotes Breast radiotherapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice.
TextSentencer_T4 477-725 Sentence denotes In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered.
TextSentencer_T5 726-921 Sentence denotes Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiotherapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization.
TextSentencer_T6 923-1043 Sentence denotes Breast radiotherapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice.
TextSentencer_T7 1044-1292 Sentence denotes In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered.
TextSentencer_T8 1293-1488 Sentence denotes Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiotherapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization.
TextSentencer_T9 1489-1804 Sentence denotes Multidisciplinary breast cancer experts at a high-volume comprehensive cancer center convened contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the application of hypofractionated and abbreviated breast radiation regimens.
TextSentencer_T10 1805-1987 Sentence denotes Substantial evidence exists to support omitting radiation among certain favorable risk subgroups of breast cancer patients and for abbreviating or accelerating regimens among others.
TextSentencer_T11 1988-2219 Sentence denotes For those who require either whole-breast or post-mastectomy radiation, with or without coverage of the regional lymph nodes, a growing body of literature supports various hypofractionated approaches that appear safe and effective.
TextSentencer_T12 2220-2507 Sentence denotes In the setting of a public health emergency with the potential to strain critical healthcare resources and place patients at infection risk, the parsimonious application of breast radiotherapy may alleviate a significant clinical burden without compromising long term oncologic outcomes.
TextSentencer_T13 2508-2658 Sentence denotes The judicious and personalized use of immature study data may be warranted in the setting of a competing mortality risk from this widespread pandemic.
TextSentencer_T14 2659-2873 Sentence denotes Breast radiotherapy (RT) is a curative component of treatment for many breast cancer presentations, albeit with limited locoregional benefit for certain patients and no survival implications for others (e.g. DCIS).
TextSentencer_T15 2874-3078 Sentence denotes 1 In the setting of the COVID-19 pandemic in which community infection represents a mortal risk, the anticipated benefit of breast RT in certain settings must be carefully weighed against infectious risk.
TextSentencer_T16 3079-3340 Sentence denotes Whereas breast cancer represents the most common non-cutaneous malignancy in the United States, limiting the overall use and duration of breast RT under conditions of extreme resource constraints is prudent and may significantly alleviate institutional burdens.
TextSentencer_T17 3341-3605 Sentence denotes Guidance from the US Centers for Disease Control and World Health Organization advise limiting the sorts of person-to-person interactions that are likely to occur in clinical spaces among patients and healthcare staff during prolonged daily fractionation regimens.
TextSentencer_T18 3606-3763 Sentence denotes In addition, healthcare resources in many settings may need to be repurposed for pandemic management such that limiting utilization is of renewed importance.
TextSentencer_T19 3764-3956 Sentence denotes Therefore, abbreviated fractionation regimens with nascent feasibility literature, as presented below, should be more strongly considered than under typically-conservative practice conditions.
TextSentencer_T20 3957-4339 Sentence denotes A team of radiation oncologists that specialize in breast cancer management at our comprehensive cancer center convened multi-disciplinary and cross-institutional contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the safe application of hypofractionated and abbreviated radiation regimens.
TextSentencer_T21 4340-4524 Sentence denotes The literature was reviewed with an emphasis on randomized controlled trial and level one evidence, followed by prospective observational studies, systematic reviews and meta-analyses.
TextSentencer_T22 4525-4617 Sentence denotes In general, the omission of radiotherapy among those who are eligible should be prioritized.
TextSentencer_T23 4618-4821 Sentence denotes These subgroups of low-risk patients have been studied in landmark trials demonstrating a moderate local control benefit of RT without improvement in already-excellent disease-specific survival outcomes.
TextSentencer_T24 4822-4849 Sentence denotes • Ductal carcinoma in situ:
TextSentencer_T25 4850-5021 Sentence denotes Prospective observational studies 2 and randomized controlled trials 3 have reproducibly demonstrated a lack of survival benefit for RT among favorable DCIS presentations.
TextSentencer_T26 5022-5196 Sentence denotes It is, therefore, advisable to forego RT for those with mammographically-detected lesions <2.5cm in size, of low-or intermediate-grade, with adequate >=2mm resection margins.
TextSentencer_T27 5197-5270 Sentence denotes 4 Caution is warranted if foregoing RT in patients under 40 years of age.
TextSentencer_T28 5271-5294 Sentence denotes 5,6 • Invasive disease:
TextSentencer_T29 5295-5576 Sentence denotes The omission of RT is preferred among those age 70 years and older who have estrogen-receptor positive (ER+) tumors that are <=3cm in size with no involved nodes (pT1-2N0M0), negative resection margins (i.e. "no tumor on ink" 7 ), and who are eligible to receive endocrine therapy.
TextSentencer_T30 5577-5681 Sentence denotes 8 A large study with limited follow-up suggests lowering this threshold to 65 years of age is also safe.
TextSentencer_T31 5682-5933 Sentence denotes 9 For patients younger than 65 years of age, ongoing studies demonstrate equipoise with regard to those who have biomarker-low disease that otherwise fits the above clinicopathologic parameters, but no mature data exist in this domain [10] [11] [12] .
TextSentencer_T32 5934-5946 Sentence denotes Delaying RT:
TextSentencer_T33 5947-6086 Sentence denotes Uncertainty surrounding the current public health emergency has made predictions about future resource allocation particularly challenging.
TextSentencer_T34 6087-6158 Sentence denotes Estimates of population-level relief range from weeks to over one-year.
TextSentencer_T35 6159-6317 Sentence denotes 13, 14 In the interest of alleviating current workload and resource constraints, evidence exists to support delaying RT among certain populations, as follows:
TextSentencer_T36 6318-6345 Sentence denotes • Ductal carcinoma in situ:
TextSentencer_T37 6346-6464 Sentence denotes In patients requiring RT for DCIS, radiation can be safely delayed up to 12 weeks following breast conserving surgery.
TextSentencer_T38 6465-6487 Sentence denotes 15 • Invasive disease:
TextSentencer_T39 6488-6771 Sentence denotes Patients with early-stage, node-negative, ER+ breast cancer can safely begin radiotherapy 8-12 weeks after breast conserving surgery without compromising disease control or survival, with several large studies showing that a delay up to 20 weeks may be safe in an appropriate subset.
TextSentencer_T40 6772-6913 Sentence denotes 16, 17 There is limited evidence to guide the interval from chemotherapy to RT, and most trials initiate RT 4-6 weeks following chemotherapy.
TextSentencer_T41 6914-7049 Sentence denotes Extrapolation from the surgical literature above suggests that an interval of up to 12 weeks from chemotherapy to RT may be reasonable.
TextSentencer_T42 7050-7255 Sentence denotes For patients with ER+ breast cancers, either DCIS or invasive, who may otherwise experience a delay or interruption in treatment, we support the prompt initiation of endocrine therapy among those eligible.
TextSentencer_T43 7256-7428 Sentence denotes There is no evidence to suggest inferior local control or survival with concurrent hormonal therapy and radiation, including both tamoxifen 18, 19 and aromatase inhibitors.
TextSentencer_T44 7429-7609 Sentence denotes 20 Though subtle differences in breast edema, fibrosis/cosmesis, and lung toxicity have been reported, the overall evidence is mixed and should not limit use of concurrent therapy.
TextSentencer_T45 7610-7659 Sentence denotes 21 Accelerated partial breast irradiation (APBI):
TextSentencer_T46 7660-7821 Sentence denotes A large body of literature, including several landmark prospective trials, has established the safety and efficacy of APBI among appropriately selected patients.
TextSentencer_T47 7822-8069 Sentence denotes This paradigm is based on the historical observation that most recurrences occur proximate to the tumor cavity, such that treatment of the tumor bed with a margin has now been shown to confer outcomes similar to whole-breast RT in select settings.
TextSentencer_T48 8070-8257 Sentence denotes Moreover, utilization of a smaller target volume allows for acceleration of the overall regimen from 3-6 weeks down to 1-2 weeks -a critical gain under resource constrained circumstances.
TextSentencer_T49 8258-8424 Sentence denotes Additional benefits may include reduced acute toxicity as evidenced by ten-year follow-up of the Florence regimen (30Gy in 5 fractions, administered every-other-day).
TextSentencer_T50 8425-8517 Sentence denotes 22 Various techniques and fractionation regimens are available for partial breast radiation.
TextSentencer_T51 8518-8671 Sentence denotes The use of brachytherapy is discouraged in the setting of strain on hospital resources, also yielding increased opportunities for exposure and infection.
TextSentencer_T52 8672-8855 Sentence denotes Accelerated external beam PBI regimens using 3D-CRT now have a large body of evidence supporting their use, with 38.5Gy in 10 fractions delivered twice-daily as a well-studied scheme.
TextSentencer_T53 8856-8996 Sentence denotes In one report, cosmesis appeared to score worse with this regimen 23 , while in the seminal US study, this appeared to be less of a concern.
TextSentencer_T54 8997-9221 Sentence denotes 24 Other well-established options for APBI include 40Gy in 10 fractions daily using 3D-CRT 25, 26 , and 30Gy in 5 fractions every-other-day using IMRT 22 (daily fractionation appears well-tolerated; personal correspondence).
TextSentencer_T55 9222-9365 Sentence denotes Meanwhile, 40Gy in 15 daily fractions to the partial breast is also an effective regimen, though is more prolonged than the other APBI options.
TextSentencer_T56 9366-9686 Sentence denotes 27 ASTRO consensus guidelines 28 and UK 29 have identified a population for which there is reasonable agreement regarding suitability of APBI: patients 50 years of age or older with screen-detected invasive disease that is <=2cm in size, ER+ and node negative, or DCIS that is low/intermediate grade and <=2.5cm in size.
TextSentencer_T57 9687-9850 Sentence denotes Of note, NSABP-B39 also included 800 patients with ER-breast cancer who exhibited excellent local control, suggesting that APBI may be reasonable among this group.
TextSentencer_T58 9851-10000 Sentence denotes Among patients who require whole-breast RT without nodal treatment, hypofractionation is the preferred standard of care in the United States 30, 31 .
TextSentencer_T59 10001-10098 Sentence denotes To that end, a number of fractionation schemes are well-supported by randomized trials including:
TextSentencer_T60 10099-10155 Sentence denotes 42.56Gy in 16 fractions 32 and 40Gy in 15 fractions 33 .
TextSentencer_T61 10156-10331 Sentence denotes Data is emerging for more extreme hypofractionation supporting 28.5Gy in 5 once-weekly fractions 34 , as well as a more accelerated daily regimen of 26Gy in 5 daily fractions.
TextSentencer_T62 10332-10516 Sentence denotes 35 Though long-term local recurrence data have not yet resulted for FAST Forward, 3year normal tissue toxicity appears equivalent to the well-tolerated three-week fractionation scheme.
TextSentencer_T63 10517-10888 Sentence denotes While various concerns have slowed widespread adoption of shorter regimens for whole-breast radiation, a number of prospective phase II, single arm and retrospective series have demonstrated efficacy and safety among groups that were previously thought to be of particular concern including: high grade tumors 36 , DCIS 37 , young age 38 or triple-negative breast cancer.
TextSentencer_T64 10889-10948 Sentence denotes 36 Post-mastectomy and/or Regional Nodal Irradiation (RNI):
TextSentencer_T65 10949-11183 Sentence denotes Analyses of the two landmark studies, MA.20 and EORTC 22922, reproducibly demonstrated that RNI reduces distant recurrence risk and significantly improves disease-free-survival, even among those with a limited axillary disease burden.
TextSentencer_T66 11184-11325 Sentence denotes 39, 40 As a result, an increasing number of patients have become eligible to receive comprehensive RNI following breast conservation or PMRT.
TextSentencer_T67 11326-11844 Sentence denotes Unfortunately, hypofractionated nodal irradiation has yet to see widespread adoption in the United States, although a nascent literature does suggest it is safe to employ 40 Gy in 15 daily fractions targeting the breast/chest wall and regional nodes (presuming the supraclavicular hotspot is below 105%; otherwise 39Gy in 15 fractions is preferred) 33, [41] [42] [43] , with ongoing studies utilizing this regimen in a randomized fashion to suggest true clinical equipoise (RT-CHARM: NCT03414970; FABREC: NCT03422103).
TextSentencer_T68 11845-12000 Sentence denotes The UK FAST FORWARD trial includes a 5fraction lymphatic RT cohort, but this is not yet considered safe outside of a trial or in the setting of palliation.
TextSentencer_T69 12001-12072 Sentence denotes Boost radiotherapy has more limited applications in emergency settings.
TextSentencer_T70 12073-12100 Sentence denotes • Ductal carcinoma in situ:
TextSentencer_T71 12101-12251 Sentence denotes The largest study to date evaluating the benefit of a boost in the setting of DCIS found a <2% local control benefit following whole breast radiation.
TextSentencer_T72 12252-12380 Sentence denotes 44 Given the absence of a survival benefit, boost can be omitted in resource-constrained settings, as was standard on RTOG 9804.
TextSentencer_T73 12381-12534 Sentence denotes 3 However, as above, caution is warranted among those younger than 40 years of ages in whom boost was shown to improve local control by 10% at 72 months.
TextSentencer_T74 12535-12557 Sentence denotes 45 • Invasive disease:
TextSentencer_T75 12558-12757 Sentence denotes Following whole breast radiation, a tumor bed boost should be considered only in the presence of significant local recurrence risk factors: ≤60 years of age, high grade tumors, or inadequate margins.
TextSentencer_T76 12758-12948 Sentence denotes 46 A standard boost after hypofractionated whole breast radiation involves 4-6 fractions, although evidence suggests that a simultaneous integrated boost may be similarly safe and effective.
TextSentencer_T77 12949-13212 Sentence denotes 47, 48 In the setting of ultra-hypofractionation with 5-fraction regimens, it is reasonable to consider a single 5.2Gy dose to the tumor bed (personal correspondence), although this fractional boost dose remains to be reported beyond the brachytherapy literature.
TextSentencer_T78 13213-13341 Sentence denotes 49 For patients receiving whole breast and nodal irradiation, a simultaneous integrated boost (SIB) can reduce treatment visits.
TextSentencer_T79 13342-13474 Sentence denotes This can be achieved with IMRT or VMAT, but is also possible with a supplemental electron field delivered with each 3D-CRT fraction.
TextSentencer_T80 13475-13601 Sentence denotes Under extreme circumstances, it may be necessary to prioritize which breast cancer patients can receive radiotherapy services.
TextSentencer_T81 13602-13699 Sentence denotes Prioritization of patients for whom RT is anticipated to provide a survival benefit is paramount.
TextSentencer_T82 13700-13818 Sentence denotes Based on available evidence and nascent clinical judgement, we have defined tiers of elevated priority (see Table 2 ).
TextSentencer_T83 13819-13989 Sentence denotes Of note, prioritization within each tier is left to the treating physicians' discretion based on patient age, comorbidities, risk of exposure and predicted benefit of RT.
TextSentencer_T84 13990-14291 Sentence denotes As governments restrict public movement to limit continued spread of the SARS-CoV-2 pandemic, radiation oncologists must now make an unprecedented calculus on behalf of our patients: the mortal risk of presenting for treatment and being exposed to infection, versus the benefit of radiotherapy itself.
TextSentencer_T85 14292-14622 Sentence denotes It therefore behooves us to consider 1) omitting radiotherapy when appropriate, 2) delaying radiation while initiating endocrine therapy in low-risk patients with ER+ breast cancer, and 3) rapidly adopting accelerated schemes when possible in a concerted effort to protect our communities and conserve scarce healthcare resources.
TextSentencer_T86 14623-14845 Sentence denotes For illustrative case presentations and guidance in contouring and planning the various regimens described above including target volumes, organs at risk, and relevant expansions, please visit http://econtour.org/hypofrac.
TextSentencer_T87 14846-14954 Sentence denotes Online cases also include dosimetric guidance and the dose constraints used in various supportive protocols.
TextSentencer_T88 14955-15177 Sentence denotes For illustrative case presentations and guidance in contouring and planning the various regimens described above including target volumes, organs at risk, and relevant expansions, please visit http://econtour.org/hypofrac.
TextSentencer_T89 15178-15322 Sentence denotes Online cases also include dosimetric guidance and the dose constraints used in various supportive protocols. • ER+ with 1-3 positive nodes (N1a)
TextSentencer_T90 15323-15342 Sentence denotes • Path N0 after NAC
TextSentencer_T91 15343-15354 Sentence denotes • LVI (NOS)
TextSentencer_T92 15355-15375 Sentence denotes • Node negative TNBC
TextSentencer_T93 15376-15404 Sentence denotes (low priority for breast RT)
TextSentencer_T94 15405-15448 Sentence denotes • Early-stage ER+ breast cancer (esp older)
TextSentencer_T95 15449-15455 Sentence denotes • DCIS
TextSentencer_T96 15456-15502 Sentence denotes • Otherwise not meeting criteria for Tiers 1-2
TextSentencer_T97 15503-15517 Sentence denotes Abbreviations:
TextSentencer_T98 15518-15618 Sentence denotes Neoadjuvant chemotherapy (NAC), triple negative breast cancer (TNBC), lymphovascular invasion (LVI).