Palliative radiotherapy for painful lymph node metastases.

BACKGROUND: There is limited evidence concerning radiotherapy for painful lymph node metastases (PLM). We evaluated the effectiveness of radiotherapy for PLM using the International Consensus Endpoint in a subgroup analysis of a prospective observational study. METHODS: In the primary study, 302 patients received radiotherapy for painful tumors. Among them, those treated with palliative radiotherapy for PLM were analyzed in the present study. We used the Brief Pain Inventory short form to evaluate the intensity of pain and the pain interference in patient's life. We collected the Brief Pain Inventory and analgesic data at baseline and at 1, 2, and 3 months after the start of radiotherapy. Pain response was assessed using the International Consensus Endpoint. Patients were diagnosed with a predominance of other pain (POP) if non-index pain of a malignant or unknown origin was present and had a greater 'worst pain' score than the index pain. RESULTS: Radiotherapy for PLM was performed on 25 patients. In total, 15 (60%) patients experienced a pain response. The pain response rates for evaluable patients were 66%, 67%, and 57% at 1-, 2-, and 3-month follow-ups, respectively. At baseline and at 1, 2, and 3 months, the median index pain scores were 7, 2, 0, and 0.5, respectively. At 1 month, all pain interference scores were significantly reduced from baseline. Four (16%) patients experienced POP within three months. CONCLUSION: Radiotherapy for PLM improved pain intensity and pain interference. Palliative radiotherapy may be a viable treatment option for PLM.

Influence of pain duration on pain outcomes following palliative radiotherapy for painful tumors: the sooner the irradiation, the better?

PURPOSE: The influence of pre-radiotherapy pain duration on post-treatment outcomes was assessed. METHODS: Patients that received palliative radiotherapy were analyzed in a prospective observational study investigating curative and palliative radiotherapy. Brief Pain Inventory data were acquired at baseline and 1, 2, and 3 months after commencing irradiation. The pain response in terms of the index pain (i.e., pain caused by the irradiated tumors) was assessed using the International Consensus Endpoint. Patients were diagnosed with predominance of other pain (POP) if non-index pain of malignant or unknown origin was present and showed a higher pain score than the index pain. Competing risk analyses were performed in which deaths without the pain endpoints were considered as competing events. RESULTS: Of 229 patients analyzed, 123 (54%) experienced a pain response and 43 (19%) experienced POP. Multivariable analyses using the Fine-Gray model revealed that patients with shorter pain duration (< 1 month) had higher cumulative incidence of pain response (subdistribution hazard ratio, 2.43; 95% confidence interval [CI], 1.35-4.38) and POP (subdistribution hazard ratio, 4.22; 95% CI, 1.30-13.70) compared with patients with longer pain duration (≥ 4 months). For patients with a pain duration of less than 1 month, cumulative incidence of pain response was estimated to be 69% (95% CI, 53-85%) and cumulative incidence of POP was estimated to be 15% (95% CI, 3-28%) at 1­month follow-up. CONCLUSION: Commencing palliative radiotherapy earlier may improve the probability of patients achieving a pain response, although POP may be more frequent.

Index and Nonindex Pain Endpoints in Radiation Therapy for Painful Tumors: A Secondary Analysis of a Prospective Observational Study.

PURPOSE: Improving pain interference in daily activities, rather than mere pain reduction, is a desirable endpoint for palliative radiation therapy. The association between pain response and pain interference has been studied almost exclusively in patients with painful bone metastases (PBMs), whereas nonindex pain has scarcely been explored in palliative radiation therapy. We investigated whether index and nonindex pain endpoints are associated with pain interference changes in patients with both PBMs and painful non-bone-metastasis tumors (PNTs). METHODS AND MATERIALS: Brief pain inventory data collected at baseline and at 2 months post-treatment were used to calculate differences in pain interference scores. Pain response in terms of the index pain was assessed using the international consensus endpoint. Patients were diagnosed with predominance of other pain (POP) if nonindex pain of malignant or unknown origin was present and had a greater pain score than the index pain. RESULTS: Of 302 patients, 127 (42%) had PBMs and 175 (58%) had PNTs. The median pain interference score, which is based on the mean of the 7 subscale items, decreased to a greater extent among responders than among nonresponders (PBM group: -3.43 vs -0.57 [P = .005]; PNT group: -2.43 vs -0.29 [P < .001]). Moreover, patients without POP experienced a greater reduction in their median pain interference score than did those with POP (PBM group: -2.71 vs +0.43 [P = .004]; PNT group: -2.00 vs +1.57 [P = .007]). The Jonckheere-Terpstra test showed a significant trend across 4 pain response categories in patients with PBMs and those with PNTs (P < .001 for both). CONCLUSIONS: The index and nonindex pain endpoints were positively and negatively associated with improvement in pain interference, respectively. There was no apparent difference between patients with PBMs and PNTs in terms of the associations of these endpoints with pain interference.

Predictors of the Predominance of NonIndex Pain After Palliative Radiation Therapy for Painful Tumors.

PURPOSE: Even when index pain (pain caused by the irradiated tumor) is palliated after radiation therapy (RT), patients may not derive the full benefits of RT in the presence of another, more intense pain. In this case-control study with prospectively collected data, we sought to identify predictors of the predominance of nonindex pain after palliative RT. METHODS AND MATERIALS: Brief Pain Inventory data were collected from patients who received RT for painful tumors. The treating radiation oncologists prospectively evaluated the intensity and origin of nonindex pain. Patients were diagnosed with predominance of other pain (POP) if nonindex pain of malignant or unknown origin was present and had a greater worst pain score than the index pain at the 1- or 2-month follow-up. Changes in pain interference from baseline to follow-up were compared between the 2 groups using Mann-Whitney U tests. Using variables that were identified as significant in a multivariable logistic regression analysis, we developed a prediction model for POP. RESULTS: Of the 170 patients who were evaluable at the 2-month follow-up, 24 (14%) were diagnosed with POP. At the 2-month follow-up examination of the patients with POP, none of the items of the pain interference scores were reduced from baseline; in contrast, patients without POP experienced significant reductions in all items. Multivariable analysis using the backward elimination method indicated that age ≤65 years, the presence of nonindex pain of malignant or unknown origin at baseline, and no opioid analgesic use at baseline were significant independent predictors of POP. As the number of the risk factors increased, the proportion of patients with POP increased. CONCLUSIONS: We identified three predictors of POP. For patients likely to have POP, careful follow-up is important, and new palliative RT or analgesics should be used when needed.

Improvement in pain interference after palliative radiotherapy for solid and hematologic painful tumors: a secondary analysis of a prospective observational study.

BACKGROUND: We previously demonstrated that patients with painful hematologic tumors were more likely to experience pain response after palliative radiotherapy (RT) than those with painful solid tumors. However, it is unknown whether change in pain interference differs between these two tumor types. In the present study, we carried out a secondary analysis of our previous prospective observational study to investigate this matter. METHODS: From patients undergoing palliative RT to treat painful tumors, Brief Pain Inventory data were collected at the start of RT and at the 1-, 2-, and 3- month follow-ups. The Mann-Whitney U test was used to compare changes in pain interference score from baseline between the two groups. RESULTS: Of the 237 patients, 203 (86%) had solid and 34 (14%) had hematologic index tumors planned to receive RT. At baseline, the groups did not differ significantly in terms of pain score, analgesic use, or pain interference score. At the 1-, 2-, and 3-month follow-ups, the changes in pain interference score from baseline did not differ significantly between the two groups. In both groups, all seven pain interference items, other than sleep in patients with hematologic tumors at the 2-month follow-up, were significantly improved (P < 0.05). CONCLUSIONS: The two groups showed comparable benefit from RT in terms of improvement in pain interference. Patients with tumor-related pain should be offered the option of palliative RT, irrespective of whether the painful tumor is solid or hematologic.

A neuropathic pain component as a predictor of improvement in pain interference after radiotherapy for painful tumors: A secondary analysis of a prospective observational study.

BACKGROUND AND PURPOSE: We previously demonstrated that patients with a tumor-related neuropathic pain component were more likely to experience a pain response after radiotherapy (RT) than those without. It is unknown whether the presence of a neuropathic component also favorably influences pain interference. In a secondary analysis of our previous prospective observational study, we investigated if the presence of a neuropathic component of the index pain caused by the irradiated tumors predicts greater reduction in pain interference. MATERIAL AND METHODS: For patients scheduled for RT for painful tumors, Brief Pain Inventory data were collected at initiation of RT and 1, 2, and 3 months thereafter. Multivariable linear regression analyses were performed to investigate the effects of the presence of a neuropathic component on the changes in pain interference scores (i.e., follow-up minus baseline). We used 10 covariates as potential confounders. RESULTS: Of the 302 analyzable patients, 93 (31%) were diagnosed as having a neuropathic component of the index pain. Multivariable linear regression analyses revealed that all the point estimates of regression coefficients at 1-, 2-, and 3-month follow-up were negative values; some were statistically significant. At 2-month follow-up, patients with a neuropathic component experienced greater reductions in their pain interference scores for walking ability (p = 0.048), normal work (p = 0.021), sleep (p = 0.001), and enjoyment of life (p = 0.010) than those without it. CONCLUSIONS: The presence of a neuropathic pain component predicted a greater reduction in pain interference after RT. Patients with neuropathic tumor-related pain should be offered the option of receiving palliative RT.

Predictors of Pain Palliation After Radiation Therapy for Painful Tumors: A Prospective Observational Study.

PURPOSE: Although radiation therapy (RT) is an important part of treatment for cancer pain, prediction of the patient's pain response remains difficult. We evaluated the characteristics of patients, their tumors, and their pain to identify the predictors of pain palliation after RT for painful tumors. METHODS: Our 3-center prospective observational study included patients scheduled for palliative or curative RT for painful tumors. Brief Pain Inventory data were collected at the start of RT and 1, 2, and 3 months thereafter. The pain response was assessed using the International Consensus Endpoint. The Mann-Whitney U-test was used to compare responders and nonresponders based on changes in the BPI scores. Predictors of the pain response were evaluated using the Fine-Gray model, in which death without a pain response was recorded as a competing risk. The independent variables were 11 a priori selected potential predictors with clinical relevance. RESULTS: Of 302 analyzable patients, 262 (87%) had solid and 40 (13%) had hematologic tumors. The median total radiation dose was 30 Gy (range, 6-70.4 Gy). The pain response rate was 52% for 264 (87%) evaluable patients at 1-, 57% for 228 (75%) such patients at 2-, and 58% for 182 (60%) evaluable patients at 3-month follow-up. At 2-month follow-up, responders experienced a greater decrease in all 7 pain interference subscales of the Brief Pain Inventory compared to nonresponders. Multivariable analysis demonstrated that hematologic tumors (hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.15-2.98), a neuropathic component of the index pain (HR, 1.50; 95% CI, 1.05-2.14), and opioid analgesic use before RT (HR, 0.65; 95% CI, 0.47-0.91) were independent significant predictors of pain response. CONCLUSIONS: Patients with hematologic tumors, a neuropathic component of the index pain, and no treatment with opioid analgesics before RT were more likely to experience pain palliation after RT.

Histopathological changes in parotid and submandibular glands of patients treated with preoperative chemoradiation therapy for oral cancer.

We retrospectively evaluated the relationship between computed tomography (CT)- and histopathological findings of parotid and submandibular glands in six patients treated for advanced oral cancer. Eligibility criteria were a pathologic diagnosis of oral squamous cell carcinoma, preoperative chemoradiation therapy (CRT) with a total dose of 30 Gy and oral S-1 (80 mg/m²/day), the availability of morphological assessments by CT and of functional assessments with the Saxon test before- and 2 weeks after CRT, and the availability of histopathological slides of irradiated parotid and submandibular glands. In the histopathological interpretation, gland structures were divided into acinar-, duct-, and adipose cells and other tissues. The Mann-Whitney test and the Spearman rank correlation test were used to determine histopathological changes. After 30-Gy irradiation, saliva production and parotid and submandibular volumes were significantly decreased (P < 0.05 each). Histopathological analysis demonstrated that 30-Gy irradiation resulted in a loss of acinar cells although acinar cells in the submandibular gland were relatively retained; the median acinar rate in the parotid and submandibular glands was 1.1% and 19.0%, respectively. The CT values after CRT were inversely correlated with adipose ratios (r = -0.98, P < 0.01) and there was a strong correlation between CT values before and after CRT (r = 0.97, P < 0.01). Our results suggested that acinar cell loss is a main contributor to changes in the volume and function of irradiated human parotid and submandibular glands. The CT value may reflect the adipose ratio rather than salivary function.

Longitudinal changes over 2 years in parotid glands of patients treated with preoperative 30-Gy irradiation for oral cancer.

OBJECTIVE: To evaluate longitudinal changes in parotid volumes and saliva production over 2 years after 30 Gy irradiation. METHODS: We retrospectively evaluated 15 assessable patients treated for advanced oral cancer. Eligibility criteria were a pathologic diagnosis of squamous cell carcinoma, preoperative radiation therapy with a total dose of 30 Gy delivered in 15 fractions, and the availability of longitudinal data of morphological assessments by computed tomography and functional assessments with the Saxon test spanning 2 years after radiation therapy. In the Saxon test, saliva production was measured by weighing a folded sterile gauze pad before and after chewing; the low-normal value is 2 g/2 min. Repeated-measures analysis of variance with Bonferroni adjustment for multiple comparisons was used to determine the longitudinal changes. RESULTS: The normalized ipsilateral parotid volumes 2 weeks and 6-, 12- and 24 months after radiation therapy were found to be 72.5, 63.7, 66.9 and 78.1%, respectively; the normalized contralateral volumes were 69.8, 64.6, 72.2 and 82.0%, respectively. The bilateral parotid volumes were significantly decreased after radiation therapy (P < 0.01). The nadir appeared at 6 months post-radiation therapy and the volumes substantially recuperated 24 months after radiation therapy (P < 0.01). Mean saliva production before radiation therapy was 3.7 g; the longitudinal changes after radiation therapy were 31.3, 38.0, 43.3 and 69.6%, respectively. Substantial recuperation of saliva production was observed 24 months after radiation therapy (P = 0.01). CONCLUSIONS: Although parotid volumes and saliva production were decreased after 30 Gy irradiation, we observed the recuperation of morphological and functional changes in the parotid glands 2 years after radiation therapy.