A feasibility study of 2-mm bolus for postmastectomy radiation therapy

    A feasibility study of two millimeter bolus for post-mastectomy radiation therapy Lauren C. Das MD, Daniel W. Golden MD, Eugenia Perevalova DMP, Anthony C. Wong MD PhD, Kimberly De Nardo R.T.(R)(T), Christopher Stepaniak PhD, Daniel S. Joyce CMD, Bradley P. McCabe PhD, Yasmin Hasan MD, Steven J. Chmura MD PhD, Anne McCall MD PII: DOI: Reference:

S1879-8500(16)30242-9 doi: 10.1016/j.prro.2016.10.015 PRRO 696

To appear in:

Practical Radiation Oncology

Received date: Revised date: Accepted date:

20 June 2016 14 October 2016 19 October 2016

Please cite this article as: Das Lauren C., Golden Daniel W., DMP Eugenia Perevalova, Wong Anthony C., De Nardo Kimberly, Stepaniak Christopher, Joyce Daniel S., McCabe Bradley P., Hasan Yasmin, Chmura Steven J., McCall Anne, A feasibility study of two millimeter bolus for post-mastectomy radiation therapy, Practical Radiation Oncology (2016), doi: 10.1016/j.prro.2016.10.015

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ACCEPTED MANUSCRIPT A feasibility study of two millimeter bolus for post-mastectomy radiation therapy Lauren C. Das MD,1 Daniel W. Golden MD,2 Eugenia Perevalova DMP,2 Anthony C. Wong MD PhD,1 Kimberly De Nardo R.T.(R)(T),2 Christopher Stepaniak PhD,2 Daniel S. Joyce CMD,2 Bradley P. McCabe PhD,2 Yasmin Hasan MD,1 Steven J. Chmura MD PhD,1 Anne McCall MD2 The Department of Radiation and Cellular Oncology, The University of Chicago Medical Center, Chicago, IL, USA; 2The Department of Radiation and Cellular Oncology, The University of Chicago Comprehensive Cancer Center at Silver Cross, New Lenox, IL, USA.

Shortened Title: 2 mm bolus for post-mastectomy radiation

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Keywords: Chest wall radiation; post-mastectomy radiation; bolus

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Corresponding Author: Lauren C. Das MD The Department of Radiation and Cellular Oncology The University of Chicago 5758 S. Maryland Avenue, MC 9006 Chicago, IL 60637 Phone 773-702-6870 Fax 773-795-4046 Email [email protected]

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Funding: This manuscript required no grant or other financial support.

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ACCEPTED MANUSCRIPT A feasibility study of two millimeter bolus for post-mastectomy radiation therapy Purpose: To prospectively evaluate the use of daily 2 mm bolus in patients undergoing post-mastectomy radiation without reconstruction using optically stimulated luminescence dosimetry (OSLD) and weekly assessment of skin

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toxicity.

Methods and Materials: We prospectively collected data from the first 49 women treated with a daily 2 mm

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SuperflabTM (Mick Radio-Nuclear Instruments, Mount Vernon, NY) bolus during their post-mastectomy radiation therapy from 2013 – 2016 at XXXX. Within the first three days of starting radiation therapy, we measured the surface

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dose in vivo at five anatomical locations under the 2 mm bolus on the chest wall. We assessed the acute skin toxicity

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during radiation weekly using the National Cancer Institute Common Toxicity Criteria (NCI CTC). Patients with reconstruction prior to radiation therapy were excluded.

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Results: Forty-nine women with a mean age of 54.3 years were treated with daily 2 mm bolus to the chest wall following mastectomy. Median follow-up was 32.7 weeks. The mean percentage of prescribed dose (standard

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deviation) for the median, central, lateral, superior, and inferior OSLDs were 100.1% (5.6%), 108.1% (6.7%), 98.1%

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(6.5%), 102.6% (8.9%), and 106.3% (6.6%) respectively. The majority (71.4%) of women experienced a maximum acute NCI CTC skin toxicity score of 2 with only 12.2% experiencing a score of 3. There were no grade 4 toxicities.

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There were no local recurrences during our follow-up period. Conclusions: Daily 2 mm bolus is a feasible regimen for chest wall bolus during post-mastectomy radiation therapy with acceptable dose build-up and skin toxicity. Keywords: Chest wall radiation; post-mastectomy radiation; bolus Shortened Title: 2 mm bolus for post-mastectomy radiation Funding: This manuscript required no grant or other financial support.

Conflicts of Interest Notification: The authors of this manuscript have no conflicts of interest to disclose. 2

ACCEPTED MANUSCRIPT INTRODUCTION The American College of Radiology has published the appropriateness criteria for post-mastectomy radiotherapy (PMRT), recommending radiotherapy for those patients with tumors greater than 5 cm in size or with at

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least four positive lymph nodes.1 Recent data has extended the use of post-mastectomy radiation for women with 1-

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3 positive axillary nodes to decrease breast cancer mortality.2 These results have increased the utilization of post-

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mastectomy radiation in the United States from 23.9% to 36.4% from 2003 to 2011.3 Despite this increase, there remains a wide variation in the practice patterns of the treatment planning and delivery of post-mastectomy

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radiation. Tissue-equivalent materials are used as a bolus to provide dose build-up along the skin and superficial chest wall in order to adequately treat any residual disease out to the skin to the full prescription dose. The bolus

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material varies widely amongst radiation oncologists. Mayadev et al. surveyed radiation oncologists within the California Athena Breast Health Network regarding the use of chest wall bolus during post-mastectomy radiation.

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Although all physicians used some material to increase the surface dose to the chest wall, 50% used a SuperflabTM

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(Mick Radio-Nuclear Instruments, Mount Vernon, NY) bolus, 50% used a different material (brass mesh, commercial bolus, custom bolus wax base), 80% used a 5 mm bolus, and 55 % used the bolus every other day.4 A survey of

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radiation oncologists in the academic and community setting also highlighted a wide variation in clinical practice.5

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One of the most common bolus regimens is applying a 5 mm tissue-equivalent bolus every other day. This technique introduces the risk of clinical error with potential failure to use the bolus on the appropriate days and also necessitates the creation of two treatment plans, which adds time and the potential for errors. Because of these pitfalls, many centers use a 5 mm or 10 mm bolus daily. However, daily bolus has been shown to lead to increased skin toxicity.6 We hypothesized that a daily 2 mm bolus would be a feasible regimen to minimize skin toxicity while eliminating the need for two radiation plans and the potential errors associated with every other day placement. We measured the skin dose using optically stimulated luminescence dosimetry (OSLD; nanoDotTM OSLD, Landauer® Inc., Glenwood, IL) and monitored the patients weekly for skin toxicity. This is a report of our first 49 patients using this technique. METHODS AND MATERIALS 3

ACCEPTED MANUSCRIPT Patient selection We evaluated the first 49 patients who received radiation to the chest wall with a daily 2 mm bolus between 2013 and 2016. This prospective study was approved by the institutional review board at XXXX. Patient

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characteristics are presented in Table 1. All patients underwent mastectomy prior to radiation and were treated with curative intent. Patients who had placement of a tissue expander, implant, or autologous tissue reconstruction were

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excluded. Patients received chemotherapy per the discretion of the treating medical oncologist with all but two patients receiving chemotherapy (Table 2).

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Radiation Treatment Planning

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Patients underwent CT simulation on a styrofoam wedge (Smithers Medical Products, Inc., North Canton, OH) with an Alpha Cradle® (Smithers Medical Products, Inc., North Canton, OH) or flat on the table with an Alpha Cradle®

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for immobilization. CT simulation was performed with 3 mm slices from the upper neck to the mid abdomen. Threedimensional treatment planning was performed using the Pinnacle treatment planning system (Pinnacle3, Philips

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Radiation Oncology Systems, Fitchburg, WI). All patients were treated with tangential photon beams for chest wall

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coverage and 93.9% of patients also were treated to their supraclavicular fossa. Supraclavicular coverage was provided in with a single anterior oblique (17.4%) or a combination of anterior and posterior oblique beams (82.6%).

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Most supraclavicular coverage was provided with a combination of 10 and 15 MV beams (82.6%). For chest wall coverage, up to 50% of the dose could be administered with 10 MV or 15 MV photons in comparison to 6 MV photons. Ten (20.4%) patients were treated with deep-inspiratory breath hold (DIBH) technique. Dose calculation was performed with a convolution-superposition algorithm. The target volume included the entire chest wall in all patients and comprehensive nodal areas in 93.9% of patients. Two millimeter thick SuperflabTM (Mick Radio-Nuclear Instruments, Mount Vernon, NY) was placed over the chest wall daily for the entire course of radiation. The bolus wrapped past the mid-axillary line. The median dose to the chest wall was 50.4 Gy (range 19.8 Gy to 51 Gy). In addition to this dose, the chest wall incision was boosted with electrons (97.8%) or photons (2.2%) in 45 (91.8%) patients. A 5 mm SuperflabTM bolus was placed for the boost.

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ACCEPTED MANUSCRIPT Radiation plans were assessed by evaluating both the dose-volume histogram and isodose lines. A maximum hot spot of 115% was allowed. Radiation techniques and doses are outlined in Table 2.

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In vivo Dosimetry

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Within three days of beginning radiation, the surface dose to the skin under the bolus was measured. For all patients except for two, OSLDs were placed at five locations on the chest wall: superior, inferior, medial, lateral and

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central (Figure 1). OSLD locations were chosen as a representative distribution of skin dose. The superior and inferior OSLDs were placed approximately midway between the medial and lateral field edges and approximately 4-5 cm

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from the superior and inferior field edges, respectively. The medial and lateral OSLDs were placed approximately

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midway between the superior and inferior field edges, and approximately 4-5 cm from the medial and lateral field edges, respectively. The center OSLD was placed on or near the scar if the scar was centrally located. The first two

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patients only had 3 OSLDs placed (medial, central, lateral). Following the placement, the OSLD (nanoDotTM OSLD, Landauer® Inc., Glenwood, IL) was processed using the MicroSTAR ii (Landauer, Inc., Glenwood, IL). OSLD

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measurements were compared to the calculated anticipated dose from the treatment plan as needed to ensure

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appropriate dose. Each OSLD reading has an error of 5% and a difference of 5% between the OSLD measurement and

Skin Toxicity

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the Pinnacle plan was deemed acceptable.

Patients were evaluated weekly for skin toxicity by one of two radiation oncologists. Skin toxicity was scored using the National Cancer Institute Common Toxicity Criteria Manual (NCI CTC). The maximum skin toxicity is reported. Photographs of skin toxicity were not routinely collected. Topical agents were prescribed at the discretion of the treating radiation oncologist. All patients were provided RadiaPlex® Rx Wound Gel Dressing (MPM Medical Inc., Irving, TX) on their first day of treatment with instructions to apply twice daily to treated areas. Aquaphor® (Beiersdorf AG, Hamburg, Germany) was added for dry desquamation and Silvadene® cream (Pfizer Inc., New York, NY) was added for moist desquamation. Patients were seen in follow-up 4-6 weeks after completing treatment to assess healing. Patients returned earlier (approximately 1-2 weeks after completion of radiation therapy) as needed to monitor skin healing. Less than 5% of patients were seen at this earlier time point. 5

ACCEPTED MANUSCRIPT Statistical Methods Grade three or greater skin toxicity was analyzed with a one-sample test of proportions (two-tail p-value)

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compared to the previously reported literature.7

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RESULTS

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Patient Characteristics

We included the first 49 women treated with daily 2 mm bolus in the current analysis (Table 1). Radiation

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was initiated at a mean of 109 days (range 28-343) after mastectomy. The median follow up after completing radiation therapy is 32.7 weeks (range 0-155 weeks). The mean age was 54.3 years (range 32.6-84.7) with the

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majority of the patients being ER positive (67.4%), PR positive (65.3%) and Her2/neu non-amplified (55.1%). All

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patients had invasive breast cancer with the exception of one patient with a malignant phyllodes tumor.

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Treatment Course

All patients completed the entirety of their planned radiation doses except for five patients. Two patients

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discontinued treatment after 19.8 Gy. These two patients included one who stopped treatment after she was found

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to have metastatic disease to bone and one who stopped treatment due to personal preference. Two patients discontinued treatment due to skin toxicity. One of these patients discontinued treatment at 54.4 Gy (out of a planned 60.4 Gy) and one patient discontinued treatment at 56 Gy (out of a planned 60 Gy). Both of these patients stopped due to grade 3 skin toxicity. An additional patient took a one-week break off of treatment after her fifth week of treatment and returned to complete her entire treatment course including a chest wall boost to 60.4 Gy. In vivo Dosimetry The OSLD measurements are shown in Table 3. The OSLD measurements show an adequate dose build-up along the chest wall immediately underneath the bolus. In general, the dose appeared to be fairly homogeneous with the exception of the superior OSLD. Skin Toxicity 6

ACCEPTED MANUSCRIPT All but two patients experienced acute skin toxicity during treatment (Table 4). The majority of patients (71.4%) experienced grade 2 acute skin toxicity. There was no grade 4 skin toxicity. A total of 6 (12.2%) patients were found to have grade 3 skin toxicity, which is statistically similar to published data of 6.25% (p=0.08).7 The timepoint at

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which the maximum acute skin toxicity was first observed is detailed in Table 5. Clinical Outcomes

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There were no chest wall recurrences during our follow-up period.

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DISCUSSION

There is significant heterogeneity amongst radiation oncologists regarding the bolus regimen and bolus

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material they prefer for post-mastectomy radiation.3 Dosimetric comparisons between different bolus regimens have been limited. One study by Ordonez-Sanz et al. compared the surface dose using 3 mm SuperflabTM, 5 mm

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SuperflabTM, brass mesh and a half-time 1 cm Vaseline® bolus using thermoluminescent dosimeters (TLD) in a

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phantom. For a 6MV plan, the average skin dose as measured by a TLD was 68% of the prescription dose for no bolus, 100.7% for Vaseline, 97.7% for 3 mm SuperflabTM, and 91.6% for brass mesh. For a 15MV plan, the TLD

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measurements were 55% of the prescription dose (no bolus), 94.2% (Vaseline), 86.5% (3 mm SuperflabTM), and 83.3%

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(brass mesh). Ordonez-Sanz et al. concluded that the 1 mm brass bolus was ideal as it required only one treatment plan, did not require modeling in the treatment planning system, resulted in superior conformity to skin surface, and did not result in as high of a skin dose as the 3 mm SuperflabTM. However, skin toxicity was not reported because experiments were performed with a phantom.8 Healy et al. described in vivo surface dose measurements of the chest wall using brass mesh, demonstrating that the surface doses ranged from 81% to 122% of the prescribed dose.7 There is also significant heterogeneity in how many fractions are delivered with a bolus in place.3 Andic et al. performed an analysis of using 1 cm bolus for 0, 5, 10, 15, 20 or 25 treatment days. They retrospectively calculated the dose volume histograms using a 3-dimensional treatment planning with the CT scans of 22 women receiving post-mastectomy radiotherapy using 1 cm bolus for 6 different consecutive treatment days. They calculated that

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ACCEPTED MANUSCRIPT using a 1 cm bolus up to 15 days of a 25 day regimen was an optimal bolus regimen, creating a mean skin structure dose of 101.9% of the prescribed dose.9 However, this study did not provide in vivo measurements. Our regimen of a daily 2 mm bolus shares many of the advantages as the daily brass mesh regimen, including

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avoiding the need for two treatment plans and excellent conformity to the skin surface. Our dosimetric outcomes are similar to those published with the skin surface receiving between 98.1 – 108.1% of the prescription dose. The lowest

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measurements tended to be near the lateral OSLD, which is expected as the beam is more en face with the bolus compared to the other fields. Similarly, the largest variation was noted with our superior OSLD, which presumably is

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due to the proximity of this OSLD to the match line for the supraclavicular field. However, specific measurements locating the OSLD in relation to the match line were not obtained. Our skin toxicity is similar to other published

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experiences including studies using brass mesh7 and 0.5 cm daily tissue-equivalent bolus,10 which both demonstrate

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that the majority of patients experience NCI CTC skin toxicity score of 1-2. The major limitations of our study are the short follow-up, relatively small patient cohort, lack of assessment

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of long-term toxicities, and lack of evaluation of skin toxicity 1-2 weeks after radiation therapy completed. The short

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follow-up limits our ability to accurately estimate long-term clinical outcomes including locoregional recurrence, overall survival, and distant metastasis free survival. Thus, our finding that there were no chest wall recurrences

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should be viewed with caution given the short follow-up period. The small patient cohort limits the generalizability of these data and does not allow for subgroup analysis. This is notable as other data supports significant variation in skin toxicity depending on other patient characteristics including race.10 Because of our short follow-up, we are unable to assess long-term toxicities, which are arguably more clinically meaningful than acute toxicities. We often counsel patients that they will likely experience acute dermatitis during treatment but not all acute toxicities develop into late toxicity. It is these late toxicities that can result in significant long-term morbidity. Other investigators have noted that maximum skin toxicity can occur 1-2 weeks after completion of radiation therapy.11 Because our patients were not evaluated at this timepoint, it is possible that our skin toxicity could be underreported. In conclusion, we demonstrate that a daily 2 mm SuperflabTM bolus is a feasible regimen for chest wall bolus in women undergoing post-mastectomy radiation therapy without reconstruction or a tissue-expander in place. This 8

ACCEPTED MANUSCRIPT regimen allows for adequate dose build-up with acceptable acute skin toxicity, and eliminates the errors associated with creating and using multiple treatment plans and every-other-day bolus use. This regimen can be viewed as a comparable alternative to other bolus regimens currently in use.

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Taylor ME, Haffty BG, Rabinovitch R, et al. ACR appropriateness criteria on postmastectomy radiotherapy expert panel on radiation oncology-breast. Int J Radiat Oncol Biol Phys. 2009;73:997-1002. Ebctcg, McGale P, Taylor C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127-2135. Yao K, Liederbach E, Lutfi W, et al. Increased utilization of postmastectomy radiotherapy in the United States from 2003 to 2011 in patients with one to three tumor positive nodes. J Surg Oncol. 2015;112:809-814. Mayadev J, Einck J, Elson S, et al. Practice patterns in the delivery of radiation therapy after mastectomy among the University of California Athena Breast Health Network. Clin Breast Cancer. 2015;15:43-47. Blitzblau RC, Horton JK. Treatment planning technique in patients receiving postmastectomy radiation therapy. Pract Radiat Oncol. 2013;3:241-248. Tieu MT, Graham P, Browne L, Chin YS. The effect of adjuvant postmastectomy radiotherapy bolus technique on local recurrence. Int J Radiat Oncol Biol Phys. 2011;81:e165-171. Healy E, Anderson S, Cui J, et al. Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh as an alternative to tissue equivalent bolus. Pract Radiat Oncol. 2013;3:e45-53. Ordonez-Sanz C, Bowles S, Hirst A, MacDougall ND. A single plan solution to chest wall radiotherapy with bolus? Br J Radiol. 2014;87:20140035. Andic F, Ors Y, Davutoglu R, Baz Cifci S, Ispir EB, Erturk ME. Evaluation of skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy. J Exp Clin Cancer Res. 2009;28:41. Wright JL, Takita C, Reis IM, Zhao W, Lee E, Hu JJ. Racial variations in radiation-induced skin toxicity severity: data from a prospective cohort receiving postmastectomy radiation. Int J Radiat Oncol Biol Phys. 2014;90:335-343. Pignol JP, Vu TT, Mitera G, Bosnic S, Verkooijen HM, Truong P. Prospective evaluation of severe skin toxicity and pain during postmastectomy radiation therapy. Int J Radiat Oncol Biol Phys. 2015;91:157-164.

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REFERENCES

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ACCEPTED MANUSCRIPT

54.3 (32.6-84.7)

Race 4 (8.2%)

Asian

2 (4.1%)

Hispanic

4 (8.2%)

Non-Hispanic Caucasian

39 (79.6%)

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African-American

30.9 (18.9-50.4)

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Mean BMI (range) Mean separation in cm (range)

25.3 (17.0-36.7)

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Smoking History

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None Former smoker

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Current smoker

Right

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Laterality Left

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Mean age in years (range)

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Patient Characteristics

30 (61.2%) 14 (28.6%) 5 (10.2%)

27 (55.1%) 22 (44.9%)

Clinical Stage Group I

11 (22.5%)

IIA

11 (22.5%)

IIB

12 (24.5%)

IIIA

7 (14.3%)

IIIB

6 (12.2%)

IIIC

0 (0%)

IV

1 (2.0%) 10

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1 (2.0%)

1b

1 (2.0%)

1c

12 (24.5%)

2

21 (42.9%)

3

7 (14.3%)

4a

0 (0%)

4b

2 (4.1%)

4c

0 (0%)

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4d

4 (8.2%)

N/A

1 (2.0%)

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Clinical N-stage

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0 1

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2a

N/A

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2b 3

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1 (2.0%)

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1a

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Clinical T-stage

21 (42.9%) 24 (49.0%) 3 (6.1%) 0 (0%) 0 (0%) 1 (2.0%)

Pathologic Stage Group 0

3 (6.1%)

IA

9 (18.4%)

IB

3 (6.1%)

IIA

6 (12.3%)

IIB

8 (16.3%)

IIIA

14 (28.6%)

IIIB

2 (4.1%) 11

ACCEPTED MANUSCRIPT IIIC

2 (4.1%)

IV

1 (2.0%)

N/A

1 (2.0%)

x(m)

1 (2.0%)

1mi

1 (2.0%)

1a

7 (14.3%)

1b

3 (6.1%)

1c

8 (16.3%)

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4 (8.2%)

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0

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Pathologic T-stage

2

15 (30.6%)

3

7 (14.3%)

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4a

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4b 4c

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4d

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N/A

0 (0%) 1 (2.0%) 0 (0%) 1 (2.0%) 1 (2.0%)

Pathologic N-stage 0

15 (30.6%)

1mi

5 (10.2%)

1a

14 (28.6%)

1b

0 (0%)

1c

1 (2.0%)

2a

11 (22.5%)

2b

0 (0%)

3a

2 (4.1%)

3b

0 (0%) 12

ACCEPTED MANUSCRIPT 3c

0 (0%)

N/A

1 (2.0%)

15 (30.6%)

Positive

33 (67.4%)

N/A

1 (2.0%)

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PR Status 16 (32.7%)

Positive

32 (65.3%)

N/A

1 (2.0%)

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Negative

Her2/neu Status Non-amplified

27 (55.1%)

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Positive

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N/A

21 (42.9%) 1 (2.0%)

45 (91.8%) 4 (8.2%)

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Positive^

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Surgical Margin Negative

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Negative

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ER Status

Table 1. Patient characteristics. BMI=Body mass index. ER=estrogen receptor. PR=progesterone receptor. Her2=human epidermal growth factor receptor. N/A=not applicable (patient was treated for a Phyllodes tumor). Clinical and pathologic staging as per AJCC, 7th Edition. ^All positive margins were either on skin or fascia except for one patient.

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ACCEPTED MANUSCRIPT Treatment Characteristics

2 (4.1%)

Neoadjuvant chemotherapy

33 (67.3%)

Adjuvant chemotherapy

15 (30.6%)

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Total RT dose (cGy) including chest wall bolus 5 (10.2%)

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5 (10.2%)

6040

37 (75.5%)

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<6000

6600 (150 cGy twice daily)

2 (4.1%)

Received chest wall boost

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No

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Yes Dose per fraction (cGy)

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150 twice daily

Tangent MV

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180 daily 200 daily

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No chemotherapy

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Received Chemotherapy

4 (8.2%) 45 (91.8%)

2 (4.1%) 41 (83.7%) 6 (12.2%)

6 MV alone

2 (4.1%)

6 MV and 10 MV

18 (36.7%)

6 MV, 10 MV, and 15 MV

27 (55.1%)

Photon/electron mixed

2 (4.1%)

Table 2. Treatment characteristics including descriptions of chemotherapy and radiation treatments. RT=radiation therapy. MV = megavoltage.

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ACCEPTED MANUSCRIPT OSLD Measurements Location of OSLD

Mean Percent of Prescribed Dose (Range; SD) 100.1% (Range 88.9% - 113.4%; SD 5.6%)

Central OSLD

108.1% (Range 97.8% - 122.7%; SD 6.7%)

Lateral OSLD

98.1% (Range 86.2% - 123.0%; SD 6.5%)

Superior OSLD

102.6% (Range 54.8% - 115.2%; SD 8.9%)

Inferior OSLD

106.3% (Range 93.7% - 128.2%; SD 6.6%)

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Median OSLD

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Table 3. Optically stimulated luminescent dosimeters (OSLD) measurements on skin underneath 2 mm chest

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wall bolus. SD=standard deviation

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ACCEPTED MANUSCRIPT Maximum Acute Skin Toxicity No skin changes

2 (4.1%)

1

Faint erythema

6 (12.2%)

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0

2

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Dry desquamation Moderate to brisk erythema

35 (71.4%)

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Patchy moist desquamation, mostly confined to skin folds and creases Moderate edema

Confluent, moist desquamation >1.5 cm in diameter and not confined to skin

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3

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folds Pitting edema Skin necrosis

0 (0%)

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4

6 (12.2%)

Ulceration of full thickness dermis

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Table 4. Maximum acute skin toxicity measured during treatment or at first follow-up. Skin toxicity was scored

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using the National Cancer Institute Common Toxicity Criteria Manual.

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ACCEPTED MANUSCRIPT Timepoint at Which Maximum Acute Skin Toxicity Was First Observed Patients (%)

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1 (2.0%)

3

6 (12.2%)

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Timepoint (weeks after starting radiation therapy)

14 (28.6%)

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6 7

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N/A

19 (38.8%) 6 (12.2%) 1 (2.0%) 2 (4.1%)

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Table 5. Timepoint at which maximum acute skin toxicity was first observed. Skin toxicity was scored using the National Cancer Institute Common Toxicity Criteria Manual. Time measured in weeks from start of radiation

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therapy. Patients were assessed weekly during treatment and at a 4-6 week follow-up. N/A = patient

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experienced no skin toxicity.

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Figure 1 Images of OSLD (optically stimulated luminescence dosimetry) placement for in vivo disimetry.

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