Support Care Cancer DOI 10.1007/s00520-013-2104-0
ORIGINAL ARTICLE
A prospective study of gastrointestinal radiation therapy-induced nausea and vomiting Michael Poon & Kristopher Dennis & Carlo DeAngelis & Hans Chung & Jordan Stinson & Liying Zhang & Gillian Bedard & Marko Popovic & Nicholas Lao & Natalie Pulenzas & Shun Wong & Edward Chow
Received: 21 October 2013 / Accepted: 12 December 2013 # Springer-Verlag Berlin Heidelberg 2014
Abstract Objective Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients’ quality of life (QOL). A prospective study among patients with GI cancers was conducted to document the timing, incidence and risk factors of radiation therapyinduced nausea and vomiting (RINV). Methods Forty-eight patients planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemoradiotherapy were followed prospectively. All episodes of nausea, vomiting, retching and antiemetic use were recorded daily for the entire treatment period and for the week following completion of therapy. QOL was assessed weekly using the Functional Living Index—Emesis Quality of Life Tool and the EORTC QLQ-C30 core questionnaire. Results Nausea occurred in 83 % of patients and emesis in 54 %. Pancreatic cancer was significantly correlated to higher proportions of nausea and emesis (p=0.002 and p=0.0003) compared to other primary sites. There were no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for nausea and emesis. Patients had significantly greater proportions of RINV during the first, M. Poon : C. DeAngelis : H. Chung : J. Stinson : L. Zhang : G. Bedard : M. Popovic : N. Lao : N. Pulenzas : S. Wong : E. Chow Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada K. Dennis Division of Radiation Oncology, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada E. Chow (*) Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5 e-mail: [email protected]
second and fifth weeks of treatment and during the first week following treatment. Vomiting was found to impair patients’ usual recreation or leisure activities and enjoyment of their meals. Worse physical, role and social functioning and greater fatigue and appetite loss over the course of treatment correlated directly with the timing of RINV symptoms. Conclusion RINV worsened QOL and was experienced even after treatment was completed; physicians should therefore be cognizant and monitor patients in the week following radiotherapy. Concomitant chemoradiotherapy should potentially be included in the moderate emetogenic risk category. Keywords Radiotherapy-induced emesis . Radiotherapy-induced nausea and vomiting . Onset timing . Concomitant chemoradiotherapy
Introduction Nausea and vomiting are common side effects of antineoplastic therapy. While supportive care of patients receiving systemic treatment has improved in the past 20 years [1], the body of research in radiotherapy-induced nausea and vomiting (RINV) remains limited in comparison to that for chemotherapy-induced nausea and vomiting (CINV). Depending on the anatomic area being irradiated, an estimated 40–80 % of patients treated with radiotherapy develop RINV [2], which can interfere with quality of life (QOL) and cause delays or interruptions of treatment [3]. Clinicians continue to underestimate the incidence of nausea, which is not as well controlled as emesis [4]. The updated ASCO antiemetic guidelines highlight RINV as an understudied area and recognize the need to improve symptom control [4]. The incidence and severity of RINV are thought to result from a combination of radiotherapy-related factors and patient-related factors [1]. These include the anatomic site of
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radiation, volume of organs such as the small bowel irradiated, radiation dose and fractionation schedule, age, gender and concurrent or recent chemotherapy [2]. However, current antiemetic guidelines categorize radiation treatments only according to the anatomic area being irradiated [1, 4]. According to antiemetic practice guidelines, radiation treatments to the upper abdomen are considered moderately emetogenic, with an estimated risk of 60–90 % [5]. The largest sources of incidence data for emetogenic risk treatments were published in a pair of Italian observational studies [2]. Across 45 Italian centres, 1,020 patients undergoing radiotherapy to all body sites were followed prospectively. Of the 52 patients who received treatment to the upper abdomen, 48 % developed nausea and 21 % developed vomiting during radiotherapy. A prior investigation by the same research group documented a 67 % nausea rate and a 38 % vomiting rate among the 42 patients receiving upper abdominal radiotherapy [6]. These results were subsequently used to support current recommendations for prophylactic antiemetic medications for upper abdominal radiotherapy. Previous studies did not compare different GI radiotherapy targets. Furthermore, they enrolled very few patients who received concomitant chemoradiotherapy which may increase the risk of nausea and vomiting experienced beyond radiotherapy alone. The effect of RINV on patients’ QOL during and following completion of radiotherapy is also unclear. Finally, radiation oncologists do not categorize treatments in terms of emetogenic potential but rather in terms of primary cancer or anatomic site. Therefore, site-specific data would be helpful to further develop antiemetic guidelines. A prospective study of RINV among patients with GI cancers was conducted to better understand and document RINV timing, incidence, natural history and risk factors, all of which are needed in order to develop personalized and appropriate supportive care strategies in the future.
Methods Patient characteristics Forty-eight patients with GI cancer that were planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemotherapy were enrolled between May and October of 2012. All patients aged 18 years or older, with a Karnofsky Performance Status (KPS) of greater than 40, and a histologically, cytologically or radiologically proven GI tumor were considered eligible. Patients who had received prior radiotherapy to brain, abdominal and/ or pelvic structures were ineligible. Antiemetic treatment plans were left to the discretion of the most responsible treating oncologists. Five patients were not included in the study herein as their treatments were cancelled prematurely.
Patient assessments Patients were followed daily from the day of their first radiation treatment to 7 days following the completion of their scheduled treatment. Patients were expected to record all episodes of nausea, vomiting, retching and antiemetic use on a diary. An individual episode was considered new only if it occurred at least 1 min following completion of the previous episode. On every treatment day, the patient met with a research assistant in-person to review all episodes of RINV. If the planned in-person meeting did not occur, attempts were made to contact the patient via telephone on the same day. QOL was assessed on a weekly basis beginning on the first day of treatment using the Functional Living Index—Emesis Quality of Life Tool (FLIE) (Appendix I) and the EORTC QLQ-C30 (QLQ-C30) core questionnaire (Appendix II). This provided a nausea and vomiting-specific QOL assessment (18-item FLIE) commonly employed in antiemetic research [7–11], while still capturing overall QOL across functional scales (30-item QLQ-C30). Patients were followed until the seventh day after their final treatment, until their treatment was cancelled prematurely or until they requested to be taken off the study. Outcomes of interest The principal outcomes of interest were: 1) The cumulative incidence of episodes of nausea and emesis from the day of the first radiation treatment to the seventh day following the last radiation treatment, inclusive. 2) The proportion of patients experiencing any episodes of nausea and emesis on an individual day. Other outcomes of interest included the frequency of episodes of nausea and emesis on a daily basis, the proportion of patients receiving antiemetic medications, the changes in QOL from baseline to the weekly assessment periods and the incidence of nausea within the 7 days following the last radiation treatment. Statistical analyses Demographic information was summarized as mean, standard deviation (SD), median and range for continuous variables and as proportions for categorical variables. The incidences of symptoms were calculated as a proportion of patients. Vomiting and retching were combined together under “emesis”. In the current study, D0 was defined as day 0 (the rest of the day following a patient’s first treatment), D1 as day 1 (the day after the first treatment) and so forth. Nausea and emetic episodes were classified into three categories to
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demonstrate frequency of events. Patients who experienced no nausea on a given calendar day were classified as “No Nausea”, 1–2 episodes of nausea were classified as “Occasional Nausea” and 3 or more episodes of nausea in a day were classified under “Frequent Nausea”. The same also applied to emetic episodes. The overall incidence of symptoms and the incidences of symptoms falling in the aforementioned categories were plotted over time. To investigate time trends of nausea and emesis, the generalized estimating equations (GEEs) methodology was employed [12]. Because the responses of RINV were ordinal variables (1=none, 2=occasional, 3=frequent), multinomial distribution with cumulative logit link function and an independent working correlation matrix were used. Independent variables included the time in days and categorical variable of period (baseline, during treatment and post-treatment). To assess significant differences between groups of patients, some categorical covariates were added in the GEE model, such as radiotherapy treatment (radiotherapy only vs. concomitant chemoradiotherapy), emetogenic risk (low vs. moderate) and primary cancer site. To investigate weekly RINV, nausea and emetic episodes were summed per patient per week and a Poisson’s distribution was used with GEE modeling to compare between weeks. General linear mixed models (GLMM) were used to investigate time trends of QOL. Natural logtransformation was applied for time-dependent QOLs. pvalues less than 0.05 were considered statistically significant. Kaplan–Meier time to events curves were plotted from baseline to first occurrence of nausea and first occurrence of emesis, respectively. Analyses were performed using the Statistical Analysis Software package (SAS version 9.3 for Windows), GENMOD and Mixed procedures.
Results Overall incidence of nausea and emesis Demographics, treatment and antiemetic details of the 48 study patients are outlined in Table 1. The mean length of time on study was 26 days (including non-treatment days) and ranged from 0 to 57 days. The most common primary sites of cancer were the pancreas (29 %), the esophagus (15 %) and the liver (15 %). All treatments had either a low or moderate emetogenic risk level as defined by MASCC/ASCO guidelines, with the majority presenting a moderate risk since the upper abdomen was irradiated (73 %; Table 1). Twenty of the patients received concurrent chemotherapy, the majority of which was considered of low emetogenic risk (85 %) [1]. Across all 48 patients, 1499 daily dairies of nausea, vomiting and retching were collected. Of the 1,499 daily symptom assessment records, 4 % of nausea records, 4 % of vomiting records and 4 % of retching records were
Table 1 Patient demographics, radiotherapy (RT), chemotherapy, and anti-emetic details Characteristic Number of patients Age (years) N Mean±SD Median (range) Karnofsky performance status N Mean±SD Median (range) Sex Female Male Primary cancer site Pancreas Esophagus Liver Colon Stomach Kidney Others Previous unrelated cancer or GI disorder/surgery No Yes Anxiety disorder No Yes Alcohol consumption No Yes Previous RT No Yes Previous chemotherapy No Yes Previous CINV No Yes RT RT duration (days) N Mean±SD Median (range) Anatomic site of RT Pancreas Liver Esophagus Upper abdomen
48 48 64.7±12.8 65 (32–92) 39 78.5±11.2 80 (60–100) 24 (50.0 %) 24 (50.0 %) 14 (29.2 %) 7 (14.6 %) 7 (14.6 %) 5 (10.4 %) 5 (10.4 %) 3 (6.2 %) 7 (14.6 %) 21 (46.6 %) 25 (54.4 %) 44 (93.6 %) 3 (6.4 %) 34 (77.3 %) 10 (22.7 %) 43 (91.5 %) 4 (8.5 %) 31 (64.6 %) 17 (35.4 %) 6 (35.3 %) 11 (64.7 %)
48 25.5±16.4 21 (0–57) 14 (29.2 %) 10 (20.8 %) 7 (14.6 %) 6 (12.5 %)
Support Care Cancer Table 1 (continued)
treatment, 60 % during post-treatment and 13 % over the entire period (Table 2).
Characteristic Stomach Pelvis Colon RT emetogenicity risk level Low Moderate RT technique IMRT Field based SBRT Conventional 3DRT Discrepancy between prescribed and received RT dose? No Yes—RT cancelled prematurely Yes—one extra fraction received Chemotherapy (CT) treatment CT planned concurrently No Yes CT received Capecitabine 5-Fluorouracil FU/Mitomycin + RT FUCISP CT emetogenicity risk level High Low Antiemetic use Antiemetic use during radiation No Yes
4 (8.3 %) 4 (8.3 %) 3 (6.25) 13 (27.1 %) 35 (72.9 %) 30 (62.5 %) 7 (20.19 %) 8 (16.7 %) 3 (6.2 %) 44 (91.6 %) 2 (4.2 %) 2 (4.2 %)
28 (58.3 %) 20 (41.7 %) 7 (35.0 %) 8 (45.0 %) 2 (10.0 %) 3 (15.0 %) 3 (15.0 %) 17 (85.0 %)
13 (27.1 %) 35 (72.9 %)
FU fluorouracil, RT radiotherapy, FUCISP fluorouracil cisplatin, IMRT intensity modulated radiotherapy, SBRT stereotactic body radiotherapy
incomplete. Antiemetic use was documented in 35 of the 48 patients and 445 daily records during the follow-up period. In these patients antiemetics were used consistently throughout treatment. However, due to the inconsistencies in patient reporting, daily antiemetic use was not analysed in relation to nausea or emetic episodes. Among all available records, 78 % and 90 % of daily symptom assessment diaries reported no nausea and emesis, respectively. Fourteen percent of events were classified as occasional nausea and 7 % as occasional emesis. Eight percent and 3 % of events were categorized as frequent for nausea and emesis, respectively. Overall, 83 % of patients experienced an episode of nausea and 54 % experienced an emetic episode. No nausea or emesis occurred in 15 % of patients during
Daily and weekly trends of nausea and emesis The daily percentage of patients experiencing nausea ranges from 0 % to 50 % and emesis values range from 0 % to 23 % (Fig. 1a, b). On any given day, an average of 22 % of patients experienced nausea and 5 % of patients experienced emesis. There were no significant overall time trends for nausea or emesis in all patients. However, significant differences can be seen for symptom experiences at different time periods. Patients had significantly more episodes of nausea during the treatment phase compared to baseline (p=0.03). In addition, patients had significantly higher proportions of emesis during treatment when compared to baseline (p=0.04) and at the post-treatment phase compared to baseline (p=0.03; Table 3). In Table 3, nausea and emesis differences between baseline and during treatment hold true when the binary covariate of radiotherapy treatment is applied to the model (p=0.03 and p= 0.04, respectively). Upon stratification, there was no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for either nausea or emesis. Patients with concurrent chemotherapy had similar proportions of both nausea and emesis over time (Fig. 1c, d). However, patients on chemotherapy had a lower probability of nausea over time (Fig. 1c). In a similar stratification for antiemetics, patients who received antiemetics had significantly higher probabilities of nausea over time (p
ORIGINAL ARTICLE
A prospective study of gastrointestinal radiation therapy-induced nausea and vomiting Michael Poon & Kristopher Dennis & Carlo DeAngelis & Hans Chung & Jordan Stinson & Liying Zhang & Gillian Bedard & Marko Popovic & Nicholas Lao & Natalie Pulenzas & Shun Wong & Edward Chow
Received: 21 October 2013 / Accepted: 12 December 2013 # Springer-Verlag Berlin Heidelberg 2014
Abstract Objective Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients’ quality of life (QOL). A prospective study among patients with GI cancers was conducted to document the timing, incidence and risk factors of radiation therapyinduced nausea and vomiting (RINV). Methods Forty-eight patients planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemoradiotherapy were followed prospectively. All episodes of nausea, vomiting, retching and antiemetic use were recorded daily for the entire treatment period and for the week following completion of therapy. QOL was assessed weekly using the Functional Living Index—Emesis Quality of Life Tool and the EORTC QLQ-C30 core questionnaire. Results Nausea occurred in 83 % of patients and emesis in 54 %. Pancreatic cancer was significantly correlated to higher proportions of nausea and emesis (p=0.002 and p=0.0003) compared to other primary sites. There were no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for nausea and emesis. Patients had significantly greater proportions of RINV during the first, M. Poon : C. DeAngelis : H. Chung : J. Stinson : L. Zhang : G. Bedard : M. Popovic : N. Lao : N. Pulenzas : S. Wong : E. Chow Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada K. Dennis Division of Radiation Oncology, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada E. Chow (*) Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5 e-mail: [email protected]
second and fifth weeks of treatment and during the first week following treatment. Vomiting was found to impair patients’ usual recreation or leisure activities and enjoyment of their meals. Worse physical, role and social functioning and greater fatigue and appetite loss over the course of treatment correlated directly with the timing of RINV symptoms. Conclusion RINV worsened QOL and was experienced even after treatment was completed; physicians should therefore be cognizant and monitor patients in the week following radiotherapy. Concomitant chemoradiotherapy should potentially be included in the moderate emetogenic risk category. Keywords Radiotherapy-induced emesis . Radiotherapy-induced nausea and vomiting . Onset timing . Concomitant chemoradiotherapy
Introduction Nausea and vomiting are common side effects of antineoplastic therapy. While supportive care of patients receiving systemic treatment has improved in the past 20 years [1], the body of research in radiotherapy-induced nausea and vomiting (RINV) remains limited in comparison to that for chemotherapy-induced nausea and vomiting (CINV). Depending on the anatomic area being irradiated, an estimated 40–80 % of patients treated with radiotherapy develop RINV [2], which can interfere with quality of life (QOL) and cause delays or interruptions of treatment [3]. Clinicians continue to underestimate the incidence of nausea, which is not as well controlled as emesis [4]. The updated ASCO antiemetic guidelines highlight RINV as an understudied area and recognize the need to improve symptom control [4]. The incidence and severity of RINV are thought to result from a combination of radiotherapy-related factors and patient-related factors [1]. These include the anatomic site of
Support Care Cancer
radiation, volume of organs such as the small bowel irradiated, radiation dose and fractionation schedule, age, gender and concurrent or recent chemotherapy [2]. However, current antiemetic guidelines categorize radiation treatments only according to the anatomic area being irradiated [1, 4]. According to antiemetic practice guidelines, radiation treatments to the upper abdomen are considered moderately emetogenic, with an estimated risk of 60–90 % [5]. The largest sources of incidence data for emetogenic risk treatments were published in a pair of Italian observational studies [2]. Across 45 Italian centres, 1,020 patients undergoing radiotherapy to all body sites were followed prospectively. Of the 52 patients who received treatment to the upper abdomen, 48 % developed nausea and 21 % developed vomiting during radiotherapy. A prior investigation by the same research group documented a 67 % nausea rate and a 38 % vomiting rate among the 42 patients receiving upper abdominal radiotherapy [6]. These results were subsequently used to support current recommendations for prophylactic antiemetic medications for upper abdominal radiotherapy. Previous studies did not compare different GI radiotherapy targets. Furthermore, they enrolled very few patients who received concomitant chemoradiotherapy which may increase the risk of nausea and vomiting experienced beyond radiotherapy alone. The effect of RINV on patients’ QOL during and following completion of radiotherapy is also unclear. Finally, radiation oncologists do not categorize treatments in terms of emetogenic potential but rather in terms of primary cancer or anatomic site. Therefore, site-specific data would be helpful to further develop antiemetic guidelines. A prospective study of RINV among patients with GI cancers was conducted to better understand and document RINV timing, incidence, natural history and risk factors, all of which are needed in order to develop personalized and appropriate supportive care strategies in the future.
Methods Patient characteristics Forty-eight patients with GI cancer that were planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemotherapy were enrolled between May and October of 2012. All patients aged 18 years or older, with a Karnofsky Performance Status (KPS) of greater than 40, and a histologically, cytologically or radiologically proven GI tumor were considered eligible. Patients who had received prior radiotherapy to brain, abdominal and/ or pelvic structures were ineligible. Antiemetic treatment plans were left to the discretion of the most responsible treating oncologists. Five patients were not included in the study herein as their treatments were cancelled prematurely.
Patient assessments Patients were followed daily from the day of their first radiation treatment to 7 days following the completion of their scheduled treatment. Patients were expected to record all episodes of nausea, vomiting, retching and antiemetic use on a diary. An individual episode was considered new only if it occurred at least 1 min following completion of the previous episode. On every treatment day, the patient met with a research assistant in-person to review all episodes of RINV. If the planned in-person meeting did not occur, attempts were made to contact the patient via telephone on the same day. QOL was assessed on a weekly basis beginning on the first day of treatment using the Functional Living Index—Emesis Quality of Life Tool (FLIE) (Appendix I) and the EORTC QLQ-C30 (QLQ-C30) core questionnaire (Appendix II). This provided a nausea and vomiting-specific QOL assessment (18-item FLIE) commonly employed in antiemetic research [7–11], while still capturing overall QOL across functional scales (30-item QLQ-C30). Patients were followed until the seventh day after their final treatment, until their treatment was cancelled prematurely or until they requested to be taken off the study. Outcomes of interest The principal outcomes of interest were: 1) The cumulative incidence of episodes of nausea and emesis from the day of the first radiation treatment to the seventh day following the last radiation treatment, inclusive. 2) The proportion of patients experiencing any episodes of nausea and emesis on an individual day. Other outcomes of interest included the frequency of episodes of nausea and emesis on a daily basis, the proportion of patients receiving antiemetic medications, the changes in QOL from baseline to the weekly assessment periods and the incidence of nausea within the 7 days following the last radiation treatment. Statistical analyses Demographic information was summarized as mean, standard deviation (SD), median and range for continuous variables and as proportions for categorical variables. The incidences of symptoms were calculated as a proportion of patients. Vomiting and retching were combined together under “emesis”. In the current study, D0 was defined as day 0 (the rest of the day following a patient’s first treatment), D1 as day 1 (the day after the first treatment) and so forth. Nausea and emetic episodes were classified into three categories to
Support Care Cancer
demonstrate frequency of events. Patients who experienced no nausea on a given calendar day were classified as “No Nausea”, 1–2 episodes of nausea were classified as “Occasional Nausea” and 3 or more episodes of nausea in a day were classified under “Frequent Nausea”. The same also applied to emetic episodes. The overall incidence of symptoms and the incidences of symptoms falling in the aforementioned categories were plotted over time. To investigate time trends of nausea and emesis, the generalized estimating equations (GEEs) methodology was employed [12]. Because the responses of RINV were ordinal variables (1=none, 2=occasional, 3=frequent), multinomial distribution with cumulative logit link function and an independent working correlation matrix were used. Independent variables included the time in days and categorical variable of period (baseline, during treatment and post-treatment). To assess significant differences between groups of patients, some categorical covariates were added in the GEE model, such as radiotherapy treatment (radiotherapy only vs. concomitant chemoradiotherapy), emetogenic risk (low vs. moderate) and primary cancer site. To investigate weekly RINV, nausea and emetic episodes were summed per patient per week and a Poisson’s distribution was used with GEE modeling to compare between weeks. General linear mixed models (GLMM) were used to investigate time trends of QOL. Natural logtransformation was applied for time-dependent QOLs. pvalues less than 0.05 were considered statistically significant. Kaplan–Meier time to events curves were plotted from baseline to first occurrence of nausea and first occurrence of emesis, respectively. Analyses were performed using the Statistical Analysis Software package (SAS version 9.3 for Windows), GENMOD and Mixed procedures.
Results Overall incidence of nausea and emesis Demographics, treatment and antiemetic details of the 48 study patients are outlined in Table 1. The mean length of time on study was 26 days (including non-treatment days) and ranged from 0 to 57 days. The most common primary sites of cancer were the pancreas (29 %), the esophagus (15 %) and the liver (15 %). All treatments had either a low or moderate emetogenic risk level as defined by MASCC/ASCO guidelines, with the majority presenting a moderate risk since the upper abdomen was irradiated (73 %; Table 1). Twenty of the patients received concurrent chemotherapy, the majority of which was considered of low emetogenic risk (85 %) [1]. Across all 48 patients, 1499 daily dairies of nausea, vomiting and retching were collected. Of the 1,499 daily symptom assessment records, 4 % of nausea records, 4 % of vomiting records and 4 % of retching records were
Table 1 Patient demographics, radiotherapy (RT), chemotherapy, and anti-emetic details Characteristic Number of patients Age (years) N Mean±SD Median (range) Karnofsky performance status N Mean±SD Median (range) Sex Female Male Primary cancer site Pancreas Esophagus Liver Colon Stomach Kidney Others Previous unrelated cancer or GI disorder/surgery No Yes Anxiety disorder No Yes Alcohol consumption No Yes Previous RT No Yes Previous chemotherapy No Yes Previous CINV No Yes RT RT duration (days) N Mean±SD Median (range) Anatomic site of RT Pancreas Liver Esophagus Upper abdomen
48 48 64.7±12.8 65 (32–92) 39 78.5±11.2 80 (60–100) 24 (50.0 %) 24 (50.0 %) 14 (29.2 %) 7 (14.6 %) 7 (14.6 %) 5 (10.4 %) 5 (10.4 %) 3 (6.2 %) 7 (14.6 %) 21 (46.6 %) 25 (54.4 %) 44 (93.6 %) 3 (6.4 %) 34 (77.3 %) 10 (22.7 %) 43 (91.5 %) 4 (8.5 %) 31 (64.6 %) 17 (35.4 %) 6 (35.3 %) 11 (64.7 %)
48 25.5±16.4 21 (0–57) 14 (29.2 %) 10 (20.8 %) 7 (14.6 %) 6 (12.5 %)
Support Care Cancer Table 1 (continued)
treatment, 60 % during post-treatment and 13 % over the entire period (Table 2).
Characteristic Stomach Pelvis Colon RT emetogenicity risk level Low Moderate RT technique IMRT Field based SBRT Conventional 3DRT Discrepancy between prescribed and received RT dose? No Yes—RT cancelled prematurely Yes—one extra fraction received Chemotherapy (CT) treatment CT planned concurrently No Yes CT received Capecitabine 5-Fluorouracil FU/Mitomycin + RT FUCISP CT emetogenicity risk level High Low Antiemetic use Antiemetic use during radiation No Yes
4 (8.3 %) 4 (8.3 %) 3 (6.25) 13 (27.1 %) 35 (72.9 %) 30 (62.5 %) 7 (20.19 %) 8 (16.7 %) 3 (6.2 %) 44 (91.6 %) 2 (4.2 %) 2 (4.2 %)
28 (58.3 %) 20 (41.7 %) 7 (35.0 %) 8 (45.0 %) 2 (10.0 %) 3 (15.0 %) 3 (15.0 %) 17 (85.0 %)
13 (27.1 %) 35 (72.9 %)
FU fluorouracil, RT radiotherapy, FUCISP fluorouracil cisplatin, IMRT intensity modulated radiotherapy, SBRT stereotactic body radiotherapy
incomplete. Antiemetic use was documented in 35 of the 48 patients and 445 daily records during the follow-up period. In these patients antiemetics were used consistently throughout treatment. However, due to the inconsistencies in patient reporting, daily antiemetic use was not analysed in relation to nausea or emetic episodes. Among all available records, 78 % and 90 % of daily symptom assessment diaries reported no nausea and emesis, respectively. Fourteen percent of events were classified as occasional nausea and 7 % as occasional emesis. Eight percent and 3 % of events were categorized as frequent for nausea and emesis, respectively. Overall, 83 % of patients experienced an episode of nausea and 54 % experienced an emetic episode. No nausea or emesis occurred in 15 % of patients during
Daily and weekly trends of nausea and emesis The daily percentage of patients experiencing nausea ranges from 0 % to 50 % and emesis values range from 0 % to 23 % (Fig. 1a, b). On any given day, an average of 22 % of patients experienced nausea and 5 % of patients experienced emesis. There were no significant overall time trends for nausea or emesis in all patients. However, significant differences can be seen for symptom experiences at different time periods. Patients had significantly more episodes of nausea during the treatment phase compared to baseline (p=0.03). In addition, patients had significantly higher proportions of emesis during treatment when compared to baseline (p=0.04) and at the post-treatment phase compared to baseline (p=0.03; Table 3). In Table 3, nausea and emesis differences between baseline and during treatment hold true when the binary covariate of radiotherapy treatment is applied to the model (p=0.03 and p= 0.04, respectively). Upon stratification, there was no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for either nausea or emesis. Patients with concurrent chemotherapy had similar proportions of both nausea and emesis over time (Fig. 1c, d). However, patients on chemotherapy had a lower probability of nausea over time (Fig. 1c). In a similar stratification for antiemetics, patients who received antiemetics had significantly higher probabilities of nausea over time (p
