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An Evaluation of Adaptive Planning by Assessing the Dosimetric Impact of Weight Loss

Throughout the Course of Radiotherapy in Bilateral Treatment of Head and Neck Cancer

Patients

Kayla Tedrick, BS, RT(T); Zach Stauch, BS, RT(T); Wes Zoller, CMD; Steve Walston, MD,

PhD; Daniel Christ, MS, DABR; Ashley Hunzeker, MS, CMD; Nishele Lenards, PhD, CMD,

RT(R)(T), FAAMD; Lee Culp, MS, CMD; Dukagjin Blakaj, MD, PhD

ABSTRACT

The purpose of this study was to investigate the dosimetric impact of weight loss in head and

neck (H&N) patients and examine the effectiveness of adaptive planning. Data was collected

from 22 H&N cancer patients who experienced weight loss during their course of radiotherapy.

The robustness of Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated

Arc Therapy (VMAT) treatment plans were compared including the potential need for re-

planning. The dosimetric impact of weight loss was evaluated by calculating a verification plan

for each patient on an assessment CT scan taken during the course of treatment. Using a

regression analysis, significance was tested for the dosimetric change in target volumes and 10

specific organs at risk (OAR) using an anatomical separation difference in the H&N at

corresponding levels. For both the IMRT and VMAT plans, a significant correlation was found

for the dose to 5% of the high risk Planning Target Volume (PTV) (D5), dose to 95% of the

intermediate risk PTV and Clinical Target Volume (CTV) (D95), and the percentage of the

pharynx receiving 65 Gy. An independent t-test was also performed for each metric in the

VMAT and IMRT plans showing the dose to 95% of the intermediate risk PTV as significant.

No quantitative method for finding the threshold of anatomical separation difference requiring a

re-plan was established. Based on the increase in dose to OAR and increased target coverage due

to separation loss, it was concluded that adaptive radiotherapy may not always be necessary, but

physician preference still prevails.

Introduction

Most H&N cancers are squamous cell carcinomas and associated with risk factors such as

tobacco and alcohol use.1 In total, there will be an estimated 51,540 new cases of oral cavity and

pharyngeal cancer in the United States in 2018, with the incidence being twice as high in males

as in females, and a 5-year survival rate of 65%.2 Standard treatments for H&N cancers often

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include radiation therapy and surgery, combined or individually, with chemotherapy when

appropriate.

Head and neck radiotherapy treatments have progressed dramatically over the past

several years. Technological advancements, such as the utilization of contrast-enhanced

diagnostic-quality CT during radiation treatment planning, has significantly contributed to this

improvement. Likewise, the use of IMRT and VMAT treatment planning and delivery have

become commonplace with external beam treatments.1 The advanced treatment techniques have

led to dose escalation and reduction of the associated toxicity for many H&N patients. Despite

these advancements, H&N radiation therapy continues to cause significant acute and long-term

side effects, such as mucositis and dysphagia, for many patients throughout the course of

treatment.

Due to the toxicities that commonly frequent H&N patients under treatment, patient

health is monitored closely by the care team during on-treatment visits. Weight loss is a common

occurrence with H&N patients due to the associated side effects. Specifically, mucositis and

dysphagia can often make it difficult for patients to maintain the proper nutritional intake without

assistance or intervention leading to an increased propensity for weight loss.3 Volumetric and

anatomic changes that may occur as a result have opened discussion on how the dosimetric

distribution may be affected to both the target areas and surrounding normal tissues.

When planning H&N treatments, the goal is to achieve prescribed target coverage while

limiting dose to local normal tissue. Specifically, there are numerous OAR in the H&N region

that are critical to avoid during radiation treatment planning in order to maintain proper function.

However, weight loss causes planned dose in normal structures to deviate as well as the dose

distribution to the defined target volumes.4 Due to these findings, re-planning of patients who

have experienced weight loss during treatment has become increasingly common. Castelli et al5

concluded that patients with a change in anatomy during treatment received an overdose of more

than 2.5 Gy to the parotid glands and weekly re-planning reduced the parotid gland mean dose

by 4 Gy. Similarly, Zhao et al6 found an increase in the maximum dose to the spinal cord and

brainstem volumes of 5.6 Gy and 2.5 Gy, respectively, by comparing repeat CT imaging to the

dose distribution on the original planning CT. As for target volumes, changes in dose distribution

have been found to be more negligible due to the use of a PTV that provides margin for error.4

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Despite these dosimetric findings, the possibility exists that re-planning is not always

required or practical. Hunter et al7 concluded that re-planning is unlikely to improve salivary

output after treatment in most cases even though re-planning can reduce the mean dose to the

parotids. This is possibly due to salivary output being dependent on the submandibular glands

and minor salivary glands as well as the parotid glands. Additionally, there has been no

definitive method established to define the amount of weight loss in the H&N region that

necessitates a re-plan. El-Sayed et al8 claimed that patients should be re-simulated and re-planned

if more than 10% of the weight loss occurs within the first 3 weeks of radiation treatment.

However, patients who were re-planned in the El-Sayed et al8 study were selected based upon

inadequate setup for daily treatment rather than specifically weight loss alone. The incorporation

of setup-related error introduces alternate dosimetric variables into consideration. As a result, a

true recommendation on when to initiate re-planning based on true anatomic loss remains

arbitrary.

Given the many resources required for re-planning and potential for treatment breaks,

there is a possibility that adaptive planning may not be the best treatment option for all patients

who have experienced weight loss. Specifically, uniform weight loss that has not adversely

affected a patient’s daily setup accuracy may not lead to significant dosimetric changes. In such a

case, it could be acceptable to continue with the original treatment plan. An investigation could

provide useful steps in determining when re-planning becomes necessary due to weight loss

alone, ultimately allowing for the establishment of weight loss parameters and re-simulation

guidelines. The objective of this retrospective study was to assess the dosimetric effects of

weight loss in H&N patients and evaluate the significance of adaptive planning.

Methods and Materials

Patient Selection & Initial Simulation Setup

Data was collected from 22 H&N cancer patients diagnosed primarily with stage II and

III squamous cell carcinoma with regional lymph node involvement. Each case was treated

definitively or postoperatively and included primary disease, as well as associated lymph node

levels bilaterally. Patients with disease of the nasopharynx were excluded from this study due to

increased emphasis on alignment of sinus cavities and base of skull versus spinal column. In the

patient population, each experienced weight loss in the H&N area throughout the course of

treatment as identified by the attending physician and treatment team on daily imaging.

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Each patient was simulated in a supine position on a GE Discovery CT scanner with a

setting of 2.5 mm slice thickness. A conformal H&N board was used for each patient.

Immobilization included either a Q-fix “Q2” with a custom headrest or a Silverman “C” headrest

with two 1 mm shims placed underneath. Long thermoplastic masks were formed for each

patient with shoulders placed inferiorly with arms at sides grasping indexed pegs placed into the

lateral aspect of the conformal H&N board (Figure 1). Patients with primary disease involving

the oral cavity were simulated with custom mouthpieces to immobilize the maxilla per

physician’s request. A knee sponge was placed underneath the legs for comfort.

Contouring

Following simulation, the patient’s CT dataset was imported into the Eclipse treatment

planning system (TPS). Organs at risk were contoured by a certified medical dosimetrist per

Radiation Therapy Oncology Group (RTOG) 1016 with few noted exceptions.9 For the purposes

of this study, the exceptions included the segmentation of the esophagus, larynx, and pharynx

structures. Specifically, the esophagus was contoured from the distal end of the pharynx to 1 cm

below the inferior portion of the PTV to include all in-field contents. The larynx was contoured

to include suprahyoid epiglottis superiorly and extend inferiorly to the level of the cricoid

cartilage. The larynx contour extended from the anterior commissure to include the arytenoids,

and the infra-hyoid region was segmented as a triangular prism shape. The pharynx included the

posterior pharyngeal wall from the base of the skull to the cricoid cartilage, including adjacent

constrictor muscles. No OAR were cropped or subtracted from target volumes for the dose

evaluation portion of this study. Immobilization contents, such as the mask and head rest, were

contoured where appropriate such that attenuation would be included in the dose calculation. The

normal tissue contours were reviewed by attending physicians.

For each patient, attending physicians contoured all target volumes. The gross tumor

volume (GTV) and CTVs were initially contoured based on the registration between the contrast-

enhanced planning CT and a diagnostic PET/CT. Segmentation of the GTV was defined to

include the primary tumor and clinically positive lymph nodes seen either on the planning CT or

pre-treatment PET imaging with a standardized uptake value (SUV) greater than 3 g/mL. The

CTV was defined to include appropriate lymph node levels based on risk-assessment by

attending physicians, as well as a standard uniform margin of 6 mm applied to GTV delineations

where appropriate. Multiple CTVs were created and separated into a high-risk volume,

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intermediate-risk volume, and low-risk volume corresponding to the prescribed dose to each; the

high-risk volume was prescribed the highest dose. For the evaluation purpose of this study,

duplicate target contours were created for ease of protocol design and labeled rCTVhigh, rCTVint,

and rCTVlow, corresponding to the originally defined risk levels and target types. For reporting

purposes, the low-risk volume contained all 3 dose levels (Figure 2). Likewise, the intermediate-

risk volume contained both the high-risk volume and intermediate-risk volume. The PTVs were

separated in the same manner as CTVs and were created by uniform expansion of the CTVs (3-5

mm) in all directions. The duplicated PTV contours were labeled rPTVhigh, rPTVint, rPTVlow. With

every patient dataset including 2-3 PTVs, the plans involved the utilization of a simultaneous

integrated boost (SIB) technique. Per the physician, the PTV and CTV volumes were permitted

to be extracted 3 mm from the external contour of the patient surface to exclude the dermis and

epidermis layers of the skin.

Treatment Planning

The original treatment plans were all planned with a VMAT method in the Eclipse TPS

and all original plans were approved by physicians. To extend the scope of this study, as well as

to compare the robustness of different planning techniques, a physician-approved 9-field sliding

window IMRT plan was created on the original planning CT for each patient, but not used

clinically. Both VMAT and IMRT plans had similar entrance angles. Due to the bilateral

involvement of disease in each patient, the arc angles chosen for the VMAT plans were a

variation of a full arc. Each treatment plan involved at least 3 arcs but no more than 4, utilizing 6

MV as the designated energy. For IMRT treatment planning, 9 fields were arranged equidistant

around the patient with 6 MV energy. Each VMAT plan was optimized in either the progressive

resolution optimizer (PRO) version 13.6.23 or the photon optimizer (PO) version 13.6.23.

Similarly, IMRT plans were optimized in PO version 13.6.23 of Eclipse. All plans were

calculated with the Acuros External Beam (AcurosXB) version 13.6.23.

The planning constraints used were established from suggestions stated in the RTOG

1016 protocol along with departmental objectives.9 The patients selected were prescribed

definitive doses by attending physicians. Of the 22 patients, 20 were prescribed 70 Gy in 35

fractions to the rPTVhigh, 63 Gy to the rPTVint, and 56 Gy to the rPTVlow to be delivered

simultaneously. The remaining 2 patients were prescribed a dose regimen of 69.96 Gy in 33

fractions to the rPTVhigh, 59.4 Gy to the rPTVint, and 54.12 Gy to the rPTVlow to be delivered

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simultaneously. All plans from the original CT datasets were normalized to ensure that 100% of

each prescription dose covered 95% of each of the individual PTVs.

Course of Treatment

Each patient started treatment as prescribed with treatment occurring once per day

Monday through Friday. Daily Cone Beam CT (CBCT) imaging was used to verify the treatment

volume and patient positioning. Each week, the patients met with the radiation oncologist’s care

team to assess side effects and discuss how treatment was progressing. At this time, the patient’s

weight was also obtained and compared to the weight recorded prior to the start of radiation

therapy treatments. The patients also met dietician for assistance in adjusting food intake if

substantial weight loss has occurred.

To evaluate whether the weight loss was resulting in loss of target coverage or increased

dose to organs at risk (OAR), patients received an assessment CT positioned in standard

treatment setup at the request of an attending physician upon analyzing daily CBCTs. In order to

narrow the focus to weight loss and eliminate other dosimetric variables involving the setup, the

patient selection criteria included those defined as having “acceptable daily positioning” based

on the registration between the original CT and the assessment CT. Specifically, “acceptable

daily positioning” was defined as having no translational shift greater than 6 mm, concentrating

on the spinal column from C1 and extending to the vertebral body representing the most inferior

in-field region of the supraclavicular target volume. The translational shifts included the left to

right, anterior to posterior, and superior to inferior directions, which were each assessed

independently.

Quantification of Weight Loss

To effectively quantify each patient’s weight loss, a metric was developed as a tool for

comparison between the original CT and assessment CT. Weight loss was defined as the

measured difference in anatomical separation between the original planning CT and the

assessment CT at various landmarks. Separations were measured at 3 vertebral levels in the

H&N: C1, C3, and the interspace of C4/C5. To collect these measurements, viewing planes were

positioned at midline of the vertebral body in the sagittal and coronal planes and positioned at the

most anterior apex of the vertebral body in the axial plane. On the viewing plane axis for each

vertebral level, 3 vectors were placed to measure separation. The first 2 vectors were drawn

diagonally, 60 apart from the central axis bifurcating the anterior apex of the vertebral body.

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These vectors were chosen to ensure that the difference in separation measured from the original

CT to the assessment CT was representative of the total circumferential loss in the H&N area.

The third vector was drawn by bifurcating the anterior apex of the vertebral body extending left

to right along the horizontal axis. This process was repeated at all 3 vertebral levels for both the

original CT and the assessment CT, measuring to the external contour of the patient habitus

(Figure 3). The measured difference between corresponding vectors of the original and

assessment CT were then recorded for all 9 vectors. Each vector was measured once with the

exception of outliers, which were confirmed. These measurements were averaged as a

quantifiable metric of weight loss for the H&N region. Likewise, the percentage weight loss at

the time of the assessment CT was recorded for each patient to establish magnitude of weight

loss.

Plan Comparisons

To assess the effects of the patients’ weight loss on the dose distribution, a verification

plan of the original VMAT and 9-field IMRT plans were calculated on the assessment CT using

all original plan parameters. Verification plans were completed by forming a rigid registration in

Eclipse (TPS) between the original planning CT and the assessment CT for each patient. Each

vertebral body was independently analyzed to ensure that all criteria were satisfied. Following

review, the translational shifts from the rigid registration were applied to the verification plan

performed on the assessment CT prior to calculation. Shift application was performed to mimic

the methodology associated with daily imaging and treatment on the linear accelerator.

Following the calculation of the verification plans on the assessment CTs, coverage to the

target volumes and dose to OAR included in the structure set were recorded and compared to the

original treatment plan. The structure set contained 10 specific OAR chosen per physician

preference based on common re-planning considerations, including: spinal cord, spinal cord

planning risk volume (PRV) with a 0.5 cm margin (rSpinalCord05), brainstem, brainstem PRV

with a 0.3 cm margin (rBrainstem03), oral cavity, parotid glands, pharynx, larynx, and esophagus.

For consistency of evaluation, nomenclature was templated as rSpinalCord, rSpinalCord05,

rBrainstem, rBrainstem03, rEsophagus, rLarynx, rPharynx, rCavityOral, and rParotids,

corresponding to each associated OAR. For segmentation of the assessment CT, the 10 identified

OAR were delineated in the same defined manner as employed during original creation including

the same contouring exceptions to the rLarynx, rPharynx, and rEsophagus contours as previously

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annotated. In addition to OAR, the original target volumes were transferred from the original CT

to the assessment CT and extracted 3 mm from the patient’s external surface to account for skin

build-up. Normal structure contours and target volumes were edited as needed and physician-

approved, including adjustments to rCTV and rPTV structures where applicable. Support

structures, including immobilization and external surface, were also re-contoured on the

assessment CT to include in the dose calculation.

The metrics evaluated were chosen with reference to RTOG 1016 and can be found in

Table 1.9 The percent difference between the metrics on the original plan CTs and the metrics on

the verification plans were then calculated for both the VMAT and 9 field IMRT plans. The need

for re-planning was assessed and the dosimetric impact of weight loss for both VMAT and

IMRT techniques was evaluated to determine if there was a difference in plan robustness

between the delivery methods as patient weight decreased.

Results

Using values generated by a dose volume histogram (DVH), statistical analysis was

performed to test for a significant correlation between all dose metrics and the total mean

separation loss at the corresponding level in the H&N area. Specifically, the spinal cord,

brainstem, pharynx, and all target metrics were assessed by total mean separation loss, which

was 1.06 cm. Whereas, the means of the larynx and esophagus were assessed by the mean

separation loss at C4/5. The mean of the oral cavity was evaluated by mean separation loss at C3,

while the mean of the parotids was evaluated by mean separation loss at C1. A regression

analysis was utilized to determine R-squared values. R-squared values indicated whether the

dependent variables, or changes in dose metrics, could be accounted for by the independent

variable, or tissue loss measurements. The statistical significance of the R-squared values were

presented as p-values in Table 2.

For both the VMAT and 9-field IMRT plans, a significant correlation was found for the

D5 of the rPTVhigh, D95 for the rPTVint, and rCTVint, and V65 of the rPharynx, as determined by the

Pearson correlation coefficients in Table 2. Regarding D5 of the rPTVhigh, a mean increase of

3.29% was found for the VMAT plans by comparing the original plan to the verification plan

(Table 3). A mean increase of 2.64% was found for the IMRT plans (Table 3). Coverage to D95

of the rPTVint escalated on average 1.37% and 0.87% for the VMAT and IMRT plans,

respectively (Table 3). The D95 of the rCTVint increased on average by 1.58% for VMAT plans

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and 1.12% for IMRT plans (Table 3). The V65 of the rPharynx increased on average 7.7% and

6.2% for the VMAT and IMRT plans, respectively (Table 4).

An independent t-test was also performed to test for a significant difference between the

VMAT and IMRT plans for each metric. T-tests are beneficial when comparing two independent

variables, in which this study was assessing changes in dose metrics to compare VMAT plans to

IMRT plans. The D95 for the rPTVint tested significant, with a mean increase of 1.37% for VMAT

versus 0.87% for IMRT plans.

Although the total mean separation loss was 1.06 cm and the mean percentage weight

loss was 9%, coverage of all targets improved on average regarding both VMAT and IMRT.

Specifically, D95 of the rPTVhigh increased 0.77% and 0.60% for VMAT and IMRT plans,

respectively (Table 3). Also, a mean increase of 1.25% and 1.01% was found for D95 of the

rCTVhigh (Table 3).

Concerning OAR, the majority of these structures also received additional dose with the

largest increase for the rPharynx. The spinal cord received a mean increase of 1.8 Gy and 1.5 Gy

for the VMAT and IMRT plans, respectively, while rBrainstem increased 0.4 Gy for VMAT and

0.2 Gy for IMRT (Table 4). Lastly, the mean of rParotids increased 4.1 Gy and 3.9 Gy for the

VMAT and IMRT plans, respectively (Figure 4, Table 4).

At the time of treatment, less than half of the patients in this study were re-planned in the

clinic. For this study, each patient’s verification plan was physician reviewed, with consideration

of the dosimetric changes to target volumes and OAR. The physician retrospectively determined

that all patients did not require a re-plan.

Discussion

Upon reviewing previous literature, the current study supports aforementioned research

that weight loss causes deviation in planned dose distribution to normal structures and target

volumes.5 Patients with separation loss in the H&N region and no setup discrepancies experience

a general increase of dose to the measured structures.6-8,10 Pair et al10 concluded that with

simulated weight loss, a considerable increase of dose to the targets and critical structures was

observed. Patients included in this study had “acceptable daily positioning” despite the loss of

tissue, and similarly experienced increased coverage of D95 and D5 for target volumes and

increase in dose to OAR.

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When strictly dealing with weight loss, an increase in source to skin distance (SSD) can

lead to less attenuation and therefore an increase in coverage for VMAT and IMRT plans.10 Pair

et al10 found that with a simulated weight loss of 1 cm, the mean dose to the target volume

increased by 2.9% and 3.6% for IMRT and VMAT plans respectively. In this study, a decrease

of 1.06 cm in total mean separation loss and subsequent increase in SSDs was found, resulting in

improved mean target coverage. The D95 of rPTVhigh increased 0.77% and 0.66% for the VMAT

and IMRT plans, respectively. The increase in SSD and average reduction in attenuation due to

weight loss could also be linked to the increase of D5.10

The correlation between separation loss and an increase to the V65 for the rPharynx could

have been influenced by inter-fractional motion and volume-based changes. A significant

volume of rPharynx was located within target structures for many patients in the current study.

Structures such as the rParotids, rEsophagus, rCavity_Oral, and rLarynx were frequently

displaced internally resulting in increased overlap with target volumes. The volumetric

transformations on the assessment CTs yielded increased dose to these overlapping portions of

measured OAR. The rPharynx consistently remained anterior to the cervical vertebral column,

which was the focal alignment structure when registering the CTs.

No significant difference was established between the VMAT and 9-field IMRT plans

aside from D95 of rPTVint. Because IMRT has less distinctive entrance angles and control points

than VMAT plans, it could be expected that IMRT would be less robust regarding weight loss

and plan quality. In a similar study, Thomson et al11 found there were no significant differences

in the change of target coverage between VMAT and IMRT plans for H&N patients who had lost

weight. Other factors could explain the minimal significant difference between the VMAT and

IMRT plans in this study, such as the asymmetric separation loss observed in the H&N patients,

with a majority of the loss observed on the lateral aspect. The weighting of the lateral control

points in VMAT plans is perhaps similar to the weighting of the lateral 280° fields in the IMRT

plans.

While a mean loss of tissue resulting in less tissue attenuation was found to cause an

increase in dose to targets and OAR, a significant correlation was not found for most metrics in

this study. The desired independent variable for this study was mean tissue separation loss in

total or at C1, C3, or C4/5; however, the possibility of confounding variables exists. For instance,

internal anatomy variations were observed in most patients, likely consequential from the

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radiation itself. Specifically, parotid glands have been found to decrease in volume during a

radiation therapy course.12-14 Teshima et al12 suggested that parotid gland shrinkage can be

radiation-induced, finding a mean decrease in volume from 68.2 to 47.9 cm3. Volume loss of the

parotid glands deemed apparent in most patients in this study. Volume reduction caused the

mean parotid dose outcome to be affected by the amount of parotid overlap with the target

volumes (Figure 4). In the cases where mean parotid dose increased due to volume reduction and

increased overlap with target volumes, re-planning may not always be advantageous. If the dose

distribution remains robust in cases of patient weight loss, the increased overlap of the parotids

may not allow for substantial mean parotid dose reduction, if target coverage is the physician’s

priority. Even with the increased overlap of the targets with the parotid glands, Hunter et al7

suggested the side effects may not be intensified.

It is essential to consider the changes in dose distribution found in this study are the

maximum projections. The verification plans that were calculated were prescribed the full course

of 35 fractions. This study is representative of a case where the weight loss occurred before the

first fraction and how dose distribution would appear if the patient were not re-planned for the

entire course of treatment. Realistically, dose variations would be much less than stated in this

study since most patients underwent their assessment CT after they had already completed over

half of the course of radiation treatments. For example, one patient’s mean parotid dose

increased by 4.44 Gy and 4.25 Gy in their VMAT and IMRT plans, respectively, but it can be

presumed the actual increase would be minimal because the assessment CT was performed on

the day of the 23rd fraction of the total 35 fractions. The collected data serves as a reference of

the average dosimetric changes to structures when weight loss occurs in H&N patients.

Re-planning assessments at this clinic include reviewing target coverage and dose to

OAR on the verification plans, with emphasis on serial organs such as the spinal cord and

brainstem. Since no rigid standards are in place, the need for a re-plan is simply based on

physician preference. In terms of this clinic’s treatment goals, each patient in this study was still

achieving appropriate coverage to the target volumes on the verification plan, in retrospect.

Despite small increases to serial organs for many patients, maximum doses remained

significantly below our clinic’s dose constraints. Due to these findings, the physician would not

have requested a re-plan for any patient in this study.

Conclusion

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Based on the increased propensity for weight loss during H&N treatment, awareness of

the volumetric and anatomic changes that may occur as a result have created debate on how the

dosimetric distribution may be affected to both the target areas and surrounding normal tissues.

The dosimetric effects that those volumetric and anatomic changes may produce were evaluated.

Significant findings included dose escalation to D95 and D5 of rPTVhigh, D5 of rCTVhigh, and V65 of

rPharynx for both VMAT and 9-field IMRT plans.

The robustness of VMAT and IMRT plans was an interest of this study, however, there

was a lack of significant difference found between the VMAT and IMRT plans. Both techniques

displayed an increase in coverage and marginal increase in dose to OAR. Loss of tissue in the

H&N area may have a greater effect on IMRT treatment plans because the amount of control

points is decreased compared to VMAT. Perhaps a larger variation could be observed, yet, this

could not be proven in this study and therefore requires more research.

Limitations in this study did exist aside from significant findings. While patients

experiencing setup issues were excluded from this study, the internal anatomy changes that were

observed in most patients were a factor. The larger overlap of rPharynx with target structures

could be of fault for the increased dose to V65. It is debatable why rSpinalCord did not also have

a strong correlation between total mean separation loss and increase in dose due to the anatomic

proximity of rPharynx and rSpinalCord. Future studies could test for a correlation using total

mean separation loss instead of the defined level of the maximum point dose. These limitations

would have to be further addressed in future studies to get a more accurate dose measurement

caused strictly by weight loss. A larger sample size would also be needed to further validate

these findings.

Re-planning may not always be necessary for a patient who has experienced weight loss

in the H&N region. While marginal changes in the dose to OAR were seen, the differences

recorded were collected by projecting the full course of treatments. However, weight loss is

gradual throughout a course of treatment and dose variations would be much less than stated in

this study, realistically, since most patients underwent their assessment CT after they had already

completed over half of the course of radiation treatments. Using the maximum projection, a

majority of the patients were still within their tolerance objectives, showing the robustness of

these VMAT and IMRT plans. No quantitative method for finding the threshold of separation

loss that requires a re-plan was established in this study. Nonetheless, the data in this study

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suggested that patients’ weight loss during the course of treatment may not always require a re-

plan, but physician preference still prevails.

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10. Pair ML, Du W, Rojas HD, et al. Dosimetric effects of weight loss or gain during volumetric

modulated arc therapy and intensity-modulated radiation therapy for prostate cancer. Med

Dosim. 2013;38(3):251-254. http://dx.doi.org/10.1016/j.meddos.2013.02.004

11. Thomson DJ, Beasley WJ, Garcez K, et al. Relative plan robustness of step-and-shoot vs

rotational intensity-modulated radiotherapy on repeat computed tomographic simulation for

weight loss in head and neck cancer. Med Dosim. 2016;41(2):154-158.

http://dx.doi.org/10.1016/j.meddos.2016.01.001

12. Teshima K, Murakami R, Tomitaka E, et al. Radiation-induced parotid gland changes in oral

cancer patients: correlation between parotid volume and saliva production. Jpn J Radiat Oncol.

2010;40(1):42-46. http://dx.doi.org/10.1093/jjco/hyp113

13. Barker JL, Garden AS, Ang KK, et al. Quantification of volumetric and geometric changes

occurring during fractionated radiotherapy for head-and-neck cancer using an integrated

CT/linear accelerator system. Int J Radiat Oncol Biol Phys. 2004;59(4):960-970.

http://dx.doi.org/10.1016/j.ijrobp.2003.12.024

14. Nishimura Y, Nakamatsu K, Shibata T, et al. Importance of the initial volume of parotid

glands in xerostomia for patients with head and neck cancers treated with IMRT. Jpn J Clin

Oncol. 2005;35(7):375-379. http://dx.doi.org/10.1093/jjco/hyi108

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Figures

Figure 1. Patient setup lying supine on the conformal head and neck board with a long aquaplast mask formed to H&N area, hands holding onto pegs, and knee sponge for comfort.

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Figure 2. High risk volume in red (rCTVhigh), intermediate risk volume in blue (rCTVint), and low risk volume in green (rCTVlow).

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Figure 3. The assessment CT overlaying the original CT with both external contours demonstrating change in tissue. The viewing planes are positioned for C3 measurement including the two diagonal vectors drawn. Also shown are the three measurements taken at C3 with the differences highlighted in green.

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Figure 4. The volume change observed in the rParotids (pink, yellow), and the increased overlap of the rParotids with the target volumes (red, blue) between the original CT (left) and the assessment CT (right).

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Tables

Table 1. Dose metrics evaluated between the original plan and verification plan for both VMAT and IMRT plans.

Structure Metric

rPTVhigh D951

rPTVhigh D51

rPTVint D95

rPTVlow D95

rCTVhigh D95

rCTVint D95

rCTVlow D95

rSpinalCord Maximum Dose

rSpinalCord05 Maximum Dose

rBrainstem Maximum Dose

rBrainstem03 Maximum Dose

rParotids Mean

rEsophagus Mean

rCavityOral Mean

rLarynx Mean

rPharynx V651

1 Dose metric D95 refers to the dose received by 95% of the target.Dose metric D5 refers to the dose received by 5% of the target.Dose metric V65 refers to the percentage of the volume receiving 65 Gy.

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Table 2. Pearson correlation coefficients of each dose metric for IMRT and VMAT plans.

Structure Dose Metric Area of AssessmentIMRT

Coefficients

VMAT

Coefficients

rPTVhigh D95 Total Mean Separation Loss 0.358 0.325

rPTVhigh D5 Total Mean Separation Loss 0.012 0.012

rPTVint D95 Total Mean Separation Loss 0.001 0.013

rPTVlow D95 Total Mean Separation Loss 0.145 0.087

rCTVhigh D95 Total Mean Separation Loss 0.363 0.409

rCTVint D95 Total Mean Separation Loss 0.017 0.037

rCTVlow D95 Total Mean Separation Loss 0.222 0.057

rSpinalCord Maximum Dose Total Mean Separation Loss 0.699 0.098

rSpinalCor

d05

Maximum Dose Total Mean Separation Loss 0.791 0.500

rBrainstem Maximum Dose Total Mean Separation Loss 0.601 0.194

rBrainstem03 Maximum Dose Total Mean Separation Loss 0.330 0.384

rParotids Mean Mean Separation Loss C1 0.343 0.337

rEsophagus Mean Mean Separation Loss C4/5 0.535 0.854

rCavityOral Mean Mean Separation Loss C3 0.870 0.727

rLarynx Mean Mean Separation Loss C4/5 0.851 0.907

rPharynx V65 Total Mean Separation Loss 0.006 0.005

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Table 3. Mean percent differences for target dose metrics for IMRT and VMAT plans and corresponding standard deviations.

Structure Dose MetricMean

Difference IMRT, (%)

Standard Deviation

IMRT, (%)

Mean Difference

VMAT, (%)

Standard Deviation

VMAT, (%)rPTVhigh D95 +0.60 +/-0.95 +0.77 +/-1.30

rPTVhigh D5 +2.64 +/-0.74 +3.29 +/-1.34

rPTVint D95 +0.87 +/-0.62 +1.37 +/-0.86

rPTVlow D95 +2.08 +/-1.13 +2.20 +/-0.96

rCTVhigh D95 +1.01 +/-0.70 +1.25 +/-1.09

rCTVint D95 +1.12 +/-0.78 +1.58 +/-0.94

rCTVlow D95 +2.36 +/-1.20 +2.52 +/-0.90

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Table 4. Mean differences for OAR dose metrics for IMRT and VMAT plans and corresponding standard deviations.

Structure Dose MetricMean

Difference IMRT, (Gy)

Standard Deviation

IMRT, (Gy)

Mean Difference

VMAT, (Gy)

Standard Deviation

VMAT, (Gy)rSpinalCord Maximum Dose +1.51 +/-1.21 +1.78 +/-1.52rSpinalCord05 Maximum Dose +3.38 +/-2.94 +3.88 +/-3.53rBrainstem Maximum Dose +0.004 +/-2.04 +0.24 +/-1.71rBrainstem03 Maximum Dose +0.59 +/-3.61 +0.41 +/-3.05rParotids Mean +3.94 +/-3.94 +4.10 +/-4.01rEsophagus Mean +0.95 +/-1.93 +1.24 +/-2.14rCavityOral Mean -0.25 +/-1.56 +0.058 +/-1.58rLarynx Mean +1.44 +/-2.39 +1.75 +/-2.40

rPharynx V65 +0.0624 (%) +/-0.0536 (%) +0.0767 (%) +/-0.0671

(%)