|Ahead of print publication
Correlation of maximum dose in PTV and the need for in-hospital supportive care during radiotherapy for H and N cancer patients
Kamal Verma1, Naveen Kumawat2, Sandeep Goel1, Subodh Chandra Pande1, Ajendra Pratap Sharma3
1 Department of Radiation Oncology, Artemis Hospitals, Gurgaon, India
2 Department of Radiation Oncology, Max Super Speciality Hospital, Saket, India
3 Department of Statistics, Artemis Hospitals, Gurgaon, India
|Date of Submission||29-Dec-2018|
|Date of Decision||15-Apr-2019|
|Date of Acceptance||19-May-2019|
|Date of Web Publication||06-Feb-2020|
Department of Radiation Oncology, Artemis Hospital, Gurgaon - 122 001, Haryana
Source of Support: None, Conflict of Interest: None
Context: An objective conformal radiotherapy treatment planning criteria that can predict severity of early effects of radiotherapy would be quite useful in reducing the side effects of radiotherapy thereby improving quality of life for head and neck cancer patients.
Aim of Study: Retrospective study aimed at correlating the maximum dose in planning target volume (PTV) with early effects of radiation.
Materials and Methods: Patients with squamous cell carcinoma of H and N region who received radical radiotherapy and concomitant chemotherapy were retrospectively analyzed for maximum dose in PTV and the requirement of gap during radiotherapy or else hospitalization for supportive care during or up to 1 month after completion of radical radiotherapy.
Results: Of a total of 23 patients, 8 patients (34.7%) required a gap of 2–14 days during their treatment. Twelve patients (52.1%) required hospitalization for 1–4 days and 4 patients (17.3%) required hospitalization for supportive care after completion of radiotherapy. The maximum dose in PTV ranged from 105.1% to 132.8% with an average of 112.68%. Subgroup analysis revealed a nonsignificant highest maximum dose of 114.72% in subset of patients requiring gap during radiotherapy (n= 8).
Conclusion: It was concluded that maximum dose in PTV is a useful predictor of need for inhospital supportive care.
Keywords: Hospitalization, maximum dose, radiotherapy
|How to cite this URL:|
Verma K, Kumawat N, Goel S, Pande SC, Sharma AP. Correlation of maximum dose in PTV and the need for in-hospital supportive care during radiotherapy for H and N cancer patients. J Can Res Ther [Epub ahead of print] [cited 2020 Apr 2]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=277833
| > Introduction|| |
In head and neck (H and N) cancer patients, locoregionally advanced disease is treated using external-beam radiotherapy with concomitant chemotherapy, and the overall survival is determined by local and/or regional recurrences. Radiotherapy aims to eradicate tumor cells in the defined target volume while sparing surrounding organs at risk (OARs) in its vicinity. There is a proven relationship between tumor dose and tumor control probability but increasing the dose also increases early as well as late effects of radiotherapy that determines the quality of life in cancer survivors. With recent advancements in the fields of patient immobilization systems, simulation and planning, and improvement in delivery techniques, most of radiotherapy centers have now shifted to the techniques such as three-dimensional conformal radiation therapy (3-D CRT).
The technique of 3-D CRT is defined as design and delivery of radiotherapy treatment plans based on 3-D image data with treatment fields individually shaped to treat only the target tissue. The aim of 3-D CRT is to achieve conformity of the high-dose region to the target volume and consequently to reduce the dose to the surrounding normal tissues. Better control on dosimetric parameters of OARs and reduction in volume of maximum doses in the target leads to lower rate of acute toxicities. Since the adverse effects of treatment can be reduced in this way, the dose to the target volume can be increased with expectation of improved cure of the tumor., In addition, 3-D-CRT allows more accurate estimates of tissue heterogeneities as well as better delineation of target volumes and OARs on the planning computerized tomography (CT) images.
The process of 3-D CRT involves simulation of patients in treatment position. Target volumes and OARs are precisely defined on these simulation images, and planning softwares are then used to evaluate numerous configurations of beam arrangement. These softwares also incorporate parameters from available beam-shaping and beam-modifying devices. When these tools are used appropriately, the volumes of OARs being irradiated are significantly reduced. Plans are assessed based on various parameters such as conformity index and homogeneity index. Achieving good conformity and homogeneity while planning for H and N cancer patients is a cumbersome process and still awaits definite parameters for objective use with a wider acceptability. Currently, there are no strict guidelines for objective assessment of these parameters, and the evaluation is largely software generated and observer dependent; this being a major concern for departments where the two-dimensional to 3-D transition is taking place.
One of the evaluation parameters is maximum dose. ICRU 50 (superseding ICRU 29) defined maximum dose as highest dose in PTV. This volume is considered clinically meaningful only if its minimum diameter exceeds 15 mm. In conventional method of planning, despite all planning efforts, there are about 10% increased doses encountered in final plans. Maximum doses (volume outside the PTV which receives dose larger than 100% of the specified PTV dose) may also be located outside PTV. We aimed to retrospectively assess the impact of maximum dose value (calculated by planning software) in predicting early effects of radiation to H and N region.
| > Materials And Methods|| |
The clinical records and dose plans of all patients diagnosed to have locoregionally advanced squamous cell carcinoma of H and N region (Stage III and IV) and treated with radiation therapy with concomitant chemotherapy were retrospectively analyzed after 1 month of completion of chemoradiotherapy. All patients were histopathologically proven by fine needle aspiration cytology or biopsy either from primary site or from draining lymph nodes. For clinical staging, AJCC staging system 2010 was used. The treatment plans were retrospectively analyzed and correlated with clinical records.
Radiotherapy technique included use of thermoplastic casts for stabilization of the head region to immobilize patient in suitable anatomical position. Proper neck supports were chosen adapting to patient's body contours with the patient lying in the supine position. The cast was extended to cover and immobilize both shoulders. In addition, shoulder strap was used wherever indicated. CT simulation was then undertaken in the same position. The upper and lower limits of the anatomic field were determined by the radiation oncologist and were marked on the individual patient with radio opaque labels with the help of laser beams. Slice thickness was 3 mm. Simulation images were transferred to planning computer by DICOM to Eclipse® planning system. The findings on clinical examination and CT and/or magnetic resonance imaging before RT were used to contour the gross tumor volumes and clinical target volumes (CTV). Appropriate margins were added to define planning target volumes (PTV). 3-D planning was undertaken with the use of various beam configurations as well as beam-shaping and beam-modifying devices. The consistency with ICRU 50 and ICRU 62 guidelines was observed. As per the policy, the planning goals were to cover 95% of the target volume with 95% of the prescribed dose and to keep the critical structure doses at or below the known tolerance limits. Radiotherapy was administered in 5 days a week fashion for a prescribed dose of 64–70 Gy with 180 cGy per fraction to 200 cGy per fraction regimens using 6MV photons. Spinal cord was shielded after a dose of 40-46 Gy using asymmetric collimator jaws. The dose planned for the posterior cervical lymphatics was boosted by APPA fields, wherever required. All of these patients also received concomitant chemotherapy along with once weekly blood counts, as per hospital policy. None of the patients received any radioprotectors during this treatment.
The 3-D CRT plans of all eligible patients were retrospectively analyzed for maximum dose. Their clinical records were reviewed for any event of hospitalization for supportive care, during or up to 1 month after completion of their course of radical chemoradiotherapy. The total number of days of hospitalization was correlated with the maximum dose in PTV as viewed in their approved radiotherapy treatment plans.
These patients were broadly divided into the following subsets:
- Patients who did not require any hospitalization
- Patients who required hospitalization during radiotherapy
- Patients who required hospitalization after completion of radical radiotherapy
- Patients who required a gap in radiotherapy due to radiation-induced mucositis.
Statistical analysis included use of mean and standard deviation for continuous data and categorical data represented as absolute numbers and percentages. Nominal categorical data between the groups were compared using Chi-square test or Fisher's exact test and used correlation coefficient to see the linear relationship.
| > Results|| |
A total of 23 patients were treated by radical chemoradiotherapy during the study period. There were 21 males and 2 females. The age group ranged from 37 to 68 years. Oral cavity (n = 8) and oropharynx (n = 8) were the two most common subsites contributing to 60% of overall cases. Other subsites included nasopharynx (n = 2), larynx (n = 2), hypopharynx (n = 2), and metastasis from unknown primary (MUO) (n = 1). All patients had locoregionally advanced disease with 87% Stage IV patients. There were no Stage I or stage II patients. The prescribed dose ranged from 6400 cGy to 7000 cGy with dose per fraction ranging from 180 cGy per fraction to 200 cGy per fraction. Due to interruption in treatment for 4 cases, the delivered dose for the group ranged from 5400 cGy to 7000 cGy. There were 11 (47.8%) who did not required any hospitalization during or after radiotherapy while 12 (52.1%) required hospitalization during radiotherapy. Four (17.3%) patients required hospitalization after completion radiotherapy and 8 (34.7%) required a gap in radiotherapy.
The highest grade of acute radiation reactions was recorded to be Grade II for a total of 12 (52.1%) patients whereas remaining nine patients (39.1%) had a maximum of Grade III reactions. Seven (30.4%) patients required a gap of more than 2 days during their treatment along with supportive care for symptomatic relief from radiation-induced mucositis. The gap varied from 2 days to 14 days with median duration of 10 days.
During the course of chemoradiotherapy, 12 patients (52.1%) required hospitalization for 1–4 days with a median of 3 days whereas 4 (17.3%) patients required hospitalization and supportive care after completion of planned course of radical chemoradiotherapy for duration of 3–7 days with a median duration of 3.5 days. The maximum dose in PTV in approved plans ranged from 105.1% to 132.8% with an average of 112.68%.
Subgroup analysis revealed that patients who did not require any hospitalization during or after radiotherapy (n = 11) had a maximum dose of 112.46% as compared to a maximum dose of 112.88% for patients requiring hospitalization during radiotherapy (n = 12), a maximum dose of 110.21% for patients requiring hospitalization after completion of radiotherapy (n = 4), and highest maximum dose of 114.72% was observed in subset of patients requiring gap during radiotherapy (n = 8). The significance level of these subgroups is depicted in [Table 1].
In the whole group, seven patients had a maximum dose exceeding 115%. These patients surprisingly neither require any gap in their radiotherapy nor they required any inhospital supportive care during the course of their chemoradiotherapy but they all had Grade III reactions and contributed to three of the eight patients that required hospitalization after completing the course of radiotherapy indicating a prolonged convalescence.
| > Discussion|| |
Because of the complex anatomy and large number of sensitive normal structures in the vicinity of a target, treatment planning for H and N cancers is a challenging task. Radiotherapy of H and N cancer has difficulties because the OARs are in close proximity to the tumor and thus a high geometrical accuracy is required. The target volume is often usually concave in shape and surrounds the spinal cord. Furthermore, parotid glands are usually near the target. Although 3-D CRT provided the means to create more conformal dose distributions through the use of complex beam arrangements, development of satisfactory treatment plans is a time-consuming process and a tedious task. Even in plans which are considered satisfactory, often the doses to critical structures come close to or exceed their tolerance levels. Further, treatment delivery-induced maximum doses in critical structures due to inter- and intra-fraction patient motion can also add to normal tissue complications and hence contribute to decreased quality of life of H and N cancer patients. Any increase in margin for PTV (planning treatment volume) is conducive to increase in side effects of treatment as well as induces inhomogeneity of dose distribution.
The treatment plans for these patients revealed that various combinations of wedge angles, number of beams, and their orientations and weightings were analyzed while planning for the patients until acceptable volumetric dose distributions were obtained. Majority of the 3-D CRT plans used a three-field technique with right and left lateral and anterior neck fields. Noncoplanar beams were also used as needed. In spite of use of all these available measures, the average maximum dose value was 112%. Usually, a value of 110% covering an area of 20 mm is considered acceptable for 3-D CRT treatment in H and N region. Any escalation beyond this is accompanied with increased incidence of radiation-related toxicities.
In this study, 65% of patients recorded Grade II radiation mucositis during their treatment. Worldwide, the incidence of radiation mucositis in patients receiving concomitant chemoradiotherapy to H and N region is reported to be about 70%.
All the patients who had a maximum dose exceeding 115% had Grade III mucositis. Although they neither require any gap in their radiotherapy nor any inhospital care, three of these eight patients required hospitalization after completing the course of radiotherapy for a median duration of 4 days. This may indicate that when maximum dose exceed 115%, patients suffer from severe acute effects and have a delayed recovery from these effects which may require inhospital care after completion of chemotherapy. These patients can be helped by increased level of supervision and supportive care during radiotherapy to avoid prolonged morbidity from acute effects.
There were 11 (47.8%) patients who did not require any hospitalization during or after radiotherapy while 12 (52.1%) patients required hospitalization during radiotherapy. Four (17.3%) patients required hospitalization after completion radiotherapy and eight patients (34.7%) required a gap in radiotherapy. An increase in maximum dose is found to be directly related to hospitalization both during and even up to 1 month after end of chemoradiotherapy. This was also quantitatively related to maximum dose, especially when the value exceeds 115%.
The maximum dose for patients requiring gap during radiotherapy was less as compared to other groups which might be due to insignificant number of patients (n = 4) in this subset. A further analysis with bigger sample size may further clarify this issue.
The severity of radiation-induced mucositis is also affected by various other factors. One of them is the use of neoadjuvant or concomitant chemotherapy. All the patients in this study received concomitant chemotherapy with Cisplatin weekly. This led to homogenization of this group with respect of effect of concomitant chemotherapy schedule.
Limitations of the study
Continuation of smoking and alcohol intake during radical radiotherapy for H and N cancer patients is associated with increase in early effects of radiation. This effect of smoking on radiation reactions could not be studied in this study because of lack of recorded information. In the institute, as per policy, all smoking patients were routinely counseled regarding benefits of smoking and alcohol cessation. The effect of nutrition and other supportive medications (steroids, antibiotics, antioxidants, minerals, and vitamin supplements) also could not be included in the analysis because these factors could not be reliably controlled while obtaining data for this study. These factors limit the external validity of this study to other groups receiving different chemotherapy regimens or supportive care. The presence of comorbidities such as diabetes mellitus is also observed to have increase in radiation-related effects. Such effects of comorbidities also were not studied in this study. Another limitation of this study is that it included patients from Stage III and IV only who require relatively larger CTV extending over to bilateral neck for most of the patients. Patients presenting with early-stage disease may require lesser volume of irradiation with more conformal fields and more homogenous plans. For such plans, the correlation of maximum dose value to severity of acute effects might not be to such an extent. The sample of study is very small and demands further trial in a controlled fashion to improve on the external validity.
It is hereby concluded that the pattern showed that an increase in maximum dose is directly related to increase in incidence of inpatient supportive care both during and even up to 1 month after end of chemoradiotherapy. This was also quantitatively related to the value of maximum dose, especially when the value exceeds 115%. Lacking the external validity, this value can be used to predict severity of acute effects of radiation, and this group of patients may be considered for increased level of supervision during chemoradiotherapy.
| > Conclusion|| |
The maximum dose value as determined by Eclipse Planning software is a useful objective parameter for prediction of severity of radiation-related events although larger study as well as its validation on other planning softwares would be even more informative.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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