|Year : 2021 | Volume
| Issue : 2 | Page : 366-371
Helical tomotherapy for prostate cancer radiation therapy: An audit of early toxicity and quality of life
Beena Kunheri1, JS Lakshmi1, Greeshma C Ravindran2, Haridas1, Vishal Marwaha3
1 Department of Radiation Oncology, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India
2 Department of Biostatistics, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India
3 Department of Amrita School of Medicine, AIMS, Amrita Vishwa Vidyapeetham, Kochi, India
|Date of Submission||08-Sep-2020|
|Date of Decision||20-Dec-2020|
|Date of Acceptance||03-Jan-2021|
|Date of Web Publication||11-Jun-2021|
Department of Radiation Oncology, Amrita School of Medicine, AIMS, Amrita Vishwa Vidyapeetham, Kochi - 682 041, Kerala
Source of Support: None, Conflict of Interest: None
Background: Radiation plays a major role in the management of localized prostate cancer (CaP). There are limited studies reporting the quality of life (QOL) and toxicity with CaP tomotherapy.
Materials and Methods: This is a single-institutional prospective observational study evaluating the acute toxicity and QOL of patients with CaP receiving tomotherapy from May 2018 to October 2019. Toxicity assessed using radiation therapy oncology group toxicity grading. QOL assessed using International Prostate Symptom Score (IPSS) and QOL score.
Results: A total number of 74 patients received radiation therapy (RT), of which 25 had postoperative RT and 49 had radical RT. The median age was 71 years. During RT, 8 (10.8%) had Grade 2 gastrointestinal (GI) and 4 (5.4%) had Grade 2 genito urinary (GU) toxicities. At 3 months, 1 (1.4%) had Grade 2 GI, 1 (1.4%) had Grade 2 GU, and 1 (1.4%) had Grade 3 GU toxicities. At 6 months, 1 patient had Grade 2 GU and no Grade 2 GI toxicity noted. In postoperative RT Group, 2 (8%) Grade 2 GI and 1 (1.4%) Grade 2 genitourinary toxicity reported during radiation. At 3 months, 1 (1.4%) Grade 2 GI, 1 (1.4%) G2 GU, and 1 (1.4%) G3 GU toxicities noted. At 6 months, no ≥ Grade 2 noted. In radical RT group, during radiation 6 (12.2%) Grade 2 GI and 3 (6.1%) Grade 2 GU recorded. At 3 and 6 months, no ≥ Grade 2 GI/GU toxicity was recorded. No Grade 3/Grade 4 observed in radical RT group. One patient in radical RT and one in postoperative RT had severe IPSS symptom score. Results are comparable to reported studies.
Conclusion: Our initial clinical experience with helical tomotherapy in CaP confirms lower rate of toxicities and no significant worsening of QOL with RT.
Keywords: Helical tomotherapy, image guided radiotherapy, prostate cancer, quality of life, toxicity
|How to cite this article:|
Kunheri B, Lakshmi J S, Ravindran GC, Haridas, Marwaha V. Helical tomotherapy for prostate cancer radiation therapy: An audit of early toxicity and quality of life. J Can Res Ther 2021;17:366-71
|How to cite this URL:|
Kunheri B, Lakshmi J S, Ravindran GC, Haridas, Marwaha V. Helical tomotherapy for prostate cancer radiation therapy: An audit of early toxicity and quality of life. J Can Res Ther [serial online] 2021 [cited 2021 Sep 23];17:366-71. Available from: https://www.cancerjournal.net/text.asp?2021/17/2/366/318107
| > Introduction|| |
Tomotherapy is an intensity-modulated rotational radiation therapy (RT) technique using photon fan beam designed for image guided radiotherapy (IGRT).,,,, In helical tomotherapy, the couch and gantry are in continuous motion and described as a helical trajectory. Thus, it permits high tailored dose distributions with excellent coverage and integrates the image guidance for patients setup verification., The additional benefit of helical tomotherapy is incorporated with adaptive planning software which determines the changes in external or internal anatomy and can modify the radiation treatment plans if necessary.
Prostate cancer (CaP) RT plays a major role in the management of localized CaP. In our center, IGRT for CaP is delivered either using volumetric arc therapy or helical tomotherapy. Majority of prostate cases are treated with helical tomotherapy. There are limited study reporting the quality of life (QOL) and toxicity pattern with different RT techniques and studies pertaining to tomotherapy are even less.
In the present study, we prospectively evaluated the acute, early delayed toxicity and QOL of patient undergoing postoperative RT (RP + RT) or radical RT for localized CaP using helical tomotherapy.
| > Materials and Methods|| |
This is a single institutional study evaluating the acute, early late toxicities and QOL of patient receiving RT for localized CaP using helical tomotherapy from May 2018 to October 2019.
Patients with age ≤85 years, with histologically confirmed nonmetastatic CaP were included in this study. Intermediate and high Risk patients received hormonal treatment as per institutional protocol. Informed consent was taken and those willing to participate in this study were given QOL questionnaires.
Simulation and planning
All patients underwent computed tomography (CT) simulation with bladder and rectal protocol (moderately filled bladder and empty rectum) in supine position with appropriate immobilization devices (head rest, knee rest, etc.,) and were treated with helical tomotherapy according to the standard institutional protocol.
Postoperative radiation dose was 60–66 Gy/30–33 fractions and in patients with gross residual disease or local relapse dose escalation was done up to 70 Gy. In radical RT intermediate risk, patients received 60 Gy in 20 fractions to prostate alone. High risk patients were treated with 70 Gy in 28 fractions to primary and pelvic nodal region received 50.4 Gy/28 fractions (SIB-simultaneous integrated boost).
Toxicity and quality of life assessment
Toxicity assessed weekly during RT and then at 3 and 6 months following RT using RT Oncology Group toxicity grading. QOL assessed pre-RT, on the last day of treatment and at 3 and 6 months following RT. QoL assessment done using International Prostate Symptom Score (IPSS) and QOL score. All patients will be followed up long term for any new toxicity and will be recorded. Compliance assessed based on treatment breaks and completion of proposed treatment. After completion, patients were reviewed every 3 months for 1st year and then every 4 months for next 1 year and thereafter every 6 months for subsequent 3 years and then annually after 5th year. This is an interim report, analyzing acute and early delayed toxicity as well as QOL. Acute toxicity is during radiation and within 3 months of treatment, early delayed toxicity is from 3 months to 6 months of treatment. Late toxicity is the toxicity after 6 months and late toxicity was not analyzed for this report.
Informed consent was obtained from all patients participating in this study.
This study was approved by the Institutional Review Board.
Statistical analysis was done using IBM SPSS 20.0 (SPSS Inc., Chicago, USA). For all continuous variables, results shown as mean ± standard deviation, and for categorical variables as percentage. To test the statistical significance of difference between the two groups Chi-square test was applied. To test the statistical significance of difference in mean QOL score between the two groups, Student's t-test was applied. P < 0.05 was considered as statistically significant.
| > Results|| |
The data of 74 patients were analyzed.
The median age was 71 years (range 51–82 years). Based on D'Amico risk stratification; 2 (2.7%) patients were low risk, 10 (13.5%) were intermediate and 62 (83.8%) were high risk. Patient characteristics are shown in [Table 1].
During RT, majority of the toxicity was reported at week 3 of RT. Thirty (40.5%) had Grade 1 and 8 (10.8%) had Grade 2 gastrointestinal (GI) toxicities. Regarding genitourinary (GU) toxicities 43 (58.1%) had Grade 1 and 4 (5.4%) had grade 2. At first follow-up (3 months), 1 (1.4%) had Grade 1, 1 (1.4%) had Grade 2 GI toxicity and none had Grade —. Regarding GU toxicity 11 (14.9%) had Grade 1 and each 1 (1.4%) patient had Grade 2/3. At 6 months, only 2 (2.7%) had Grade 1 GI, 4 (5.4%) had Grade 1 GU and 1 (1.4%) had Grade 3 GU toxicities. Overall no Grade 3 or 4 GI toxicity and no grade 4 GU toxicity were observed. [Figure 1] shows the overall toxicity pattern in my cohort.
|Figure 1: Overall toxicity pattern in prostate patients in helical tomotherapy|
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Of the 74 patient, 25 (33.8%) patients received postoperative RT and 49 (66.2%) received Radical RT. On subgroup analysis with regards to postoperative RT patients, 12 (48%) had Grade 1 and 2 (8%) had Grade 2 GI toxicities. Regarding GU toxicity 19 (76%) had Grade 1 and 1 (4%) had Grade 2. At 3 months, 1 (4.5%) patient had Grade 2 GI and each 1 (4.5%) had Grade 2/3 had GU toxicity. At 6 months, no Grade 2 toxicity was recorded. [Figure 2] shows the toxicity pattern in adjuvant/salvage RT patients. With regards to radical RT, during RT 18 patients (36.7%) had Grade 1 and 6 (12.2%) had Grade 2 GI toxicity. With regards to GU toxicity 24 (49%) had Grade 1 and 3 (6.1%) patients had Grade 2. At 3 months and 6 months, no Grade 2 GI toxicity was recorded. Overall, no grade 3 or 4 GI and GU toxicity were observed. [Figure 3] shows the toxicity pattern in radical RT patients.
|Figure 2: Toxicity pattern in postoperative radiation therapy patients in helical tomotherapy|
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|Figure 3: Toxicity pattern in radical radiation therapy patients in helical tomotherapy|
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Quality of life
QOL assessment done at baseline (before starting RT), at RT completion, at 3 months and at 6 months. IPSS symptom score and IPSS QOL scale were used for assessment. For analysis, IPSS QOL scale categorization done as good and average to severe. “Good” includes delighted, pleased, and mostly satisfied. “Average” includes mixed and “Poor” includes mostly dissatisfied, unhappy, and terrible.
International Prostate Symptom Score symptom score
No severe symptoms were noted at baseline. One (1.4%) patient had severe symptom score at the time of RT completion and 3 months. No severe symptoms noted at 6 months. On subgroup analysis, in postoperative patients, one patient had severe symptom at RT completion and at 3 months whereas in radical RT patients no severe symptom score noted at RT completion, at 3 months and at 6 months.
International Prostate Symptom Score quality of life score
One patient in the radical RT arm had poor QOL at RT completion. No poor QOL score noted at 3 months and at 6 months.
IPSS symptom and QOL score is shown in [Table 2] and [Table 3].
|Table 2: Overall international prostate symptom score symptom score and quality of life score|
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|Table 3: International prostate symptom score symptom score and quality of life score of postoperative radiation therapy and radical radiation therapy patients|
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| > Discussion|| |
Helical tomotherapy is an advanced form of IGRT delivery system with onboard imaging and capability of adaptive planning., Our clinical experience with moderate hypofractionation in carcinoma prostate patients using helical tomotherapy show low rate of toxicity with no marked deterioration in QOL. With the benefit of image guidance and adaptive planning software in tomotherapy, lower and acceptable rate of toxicities were achievable which translates into better QOL. This study reports the acute toxicity and QOL. Late toxicity will be reported later after adequate follow-up.
As mentioned in the literature, the most common toxicities are GI and GU in CaP patients. Patients receiving postoperative RT are expected to have more toxicities as two radical modalities of treatment are combined. After the advent of modern RT techniques (IGRT) and following advancement in surgical techniques, there is a significant reduction in the toxicities compared to conventional methods. Beck et al. in 2017, analyzed the toxicity pattern of 69 patients receiving adjuvant/salvage RT using Tomotherapy technique, reported 10.1%(n = 7) GU and 5.8% (n = 4) GI acute toxicities. Similarly, Linsay et al. in 2017, evaluated the toxicity pattern of 313 patients receiving adjuvant RT using helical tomotherapy reported 25% (n = 77) Grade 2 GU and 33% (n = 103) Grade 2/1% (n = 1) Grade 3 GI acute toxicities. The literature on hypofractionated postoperative helical tomotherapy in CaP by Cuccia et al.[12-15] report the various helical tomotherapy fractionation schemes. Acute GI and GU toxicities were reported. These include: For GU Grade 1 in 46% (n = 35) and Grade 2 in 4% (n = 3). For GI toxicities, Grade 1 in 36% (n = 75) and Grade 2 in 18% (n = 14). In the present study, we observed low rate of acute and early delayed toxicity. During RT, 8% patients had Grade 2 GI and 4% had Grade 2 GU toxicity. At 3 months, 4.5% had Grade 3 GI and 4.5% grade 2 GU and 4.5% had Grade 3 GU toxicities. At 6 months, no Grade 2, 3, or 4 toxicities were recorded. Low rates of toxicities observed in the present study could be due to advanced techniques such as Helical Tomotherapy and minimally invasive surgery, robotic-assisted radical prostatectomy. We also used a tighter margin of 0.5 cm from CTV to PTV, which is considered minimum recommended when daily online image guidance adopted. [Table 4] shows the CaP studies and related toxicity pattern following image-guided RT.
Due to the increasing workload and logistic issues in a country like India, it becomes important to reduce treatment time whenever possible. CaP with low α/β value is one tumor that can be treated using hypofractionation. Long-term follow-up results of hypofractionated studies such as conventional versus hypofractionated high-dose intensity-modulated radiotherapy for CaP -CHHIP (60 Gy in 20 fractions) and Cleveland clinic dose schedules (70 Gy in 28 fractions) did show improved control rates with acceptable toxicity. CHHIP trial used IMRT to compare conventional versus hypofractionation in 3162 men. They reported 38% Grade 2 or more GI and 49% Grade 2 or more GU acute toxicities. At 18 weeks, they noted decreasing trend; 3% GI and 5%GU toxicities were reported. Cleveland clinic data on hypofractionation ((70 Gy in 28 fractions) with IGRT reported 40% Grade 1 and 9% Grade 2 GI toxicity. GU toxicities were 48% Grade 1, 18% Grade 2, and 1% Grade 3. Barra et al. in 2014, reported 36% Grade 1, 13% Grade 2, 4% Grade 3 GU toxicities and 6% Grade 1, 4% Grade 2 GI toxicities using helical tomotherapy in CaP patients receiving radical radiotherapy. In this study, we observed 12.2% Grade 2 GI and 6.1% Grade 2 GU toxicity. At 3 months and 6 months, no Grade 2 or more GI/GU toxicity was recorded. The low rates of toxicity could be attributed to the high conformality achieved in our plans thereby limiting the dose to the organs at risk (OARs). We need further follow-up and larger cohort to confirm the absolute benefit and outcome.
Quality of life assessment
QOL is an important hallmark in CaP management, especially considering that men are likely to survive for a considerable number of years after treatment. The CaP Outcomes Study on QOL examined 1,655 men in 1994–1995 and who underwent either radical prostatectomy (1,164 men) or radiotherapy (491 men). The study found that those undergoing surgery were significantly more likely to have urinary incontinence and erectile dysfunction (ED) at 2 and 5 years. However, bowel urgency at 2 and 5 years were significantly more in those undergoing radiotherapy. Notably, when the follow-up duration was extended to 15 years, the burden of urinary incontinence, ED, and bowel urgency were comparable between the treatment modalities. A systematic review and meta-analysis by Chen et al. reported a pooled analysis of total 6 studies containing 4423 patients. They analyzed the QOL between RP and RT patients and concluded that RP was associated with worse urinary and sexual domain score than EBRT. In contrast, EBRT group had lower bowel domain score than RP group. Pervez et al. reported the QOL outcome of CaP patients treated with tomotherapy in 2012. The study found that bowel functions were affected maximum than urinary symptoms. Bowel symptoms scores declined at 1 and 6 months compared to baseline whereas overall urinary scores at baseline with those at 1 month and 6 months showed improvement. In the present study, we observed improvement in both IPSS symptom score and QOL score on completion of RT, at 3 months and at 6 months compared to baseline in the radical RT group. On subgroup analysis, radical RT patients had better QOL as compared to postoperative RT patients on follow-up. In the postoperative RT group, one patient had severe IPSS score during RT whereas no patient had severe score in the radical RT arm. The improvement in QOL noticed for radical RT patients compared to base line could be due to the bulky local disease responding to treatment. The subjective nature of questionnaires and attitude of the patients toward their QOL and the timing does affect the response to the questionnaire.
This is a short-term study analyzing acute toxicity and health-related QOL issues. Longer follow-up is needed to evaluate the late effects, outcome, and long-term bearing on QOL.
| > Conclusion|| |
Our clinical experience with helical tomotherapy in CaP RT confirms lower rate of toxicities and no deterioration in QOL as compared with studies in literature.,,,, The use of IGRT and highly conformal treatment lowers the toxicity rates in both radical RT and postoperative RT as it allows more uniform coverage of target, while minimizing OARs doses improving the therapeutic ratio.
We would like to thank all the staff of the Department of Radiation oncology, Medical Oncology, Uro-oncology.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]