Is immunotherapy at reduced dose and radiotherapy for older patients with locally advanced non-small lung cancer feasible?-a narrative review by the international geriatric radiotherapy group.

Background and Objective: The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.

Image-guided radiotherapy and -brachytherapy for cervical cancer.

Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer.

Potential applications of image-guided radiotherapy for radiation dose escalation in patients with early stage high-risk prostate cancer.

Patients with early stage high-risk prostate cancer (prostate specific antigen > 20, Gleason score > 7) are at high risk of recurrence following prostate cancer irradiation. Radiation dose escalation to the prostate may improve biochemical-free survival for these patients. However, high rectal and bladder dose with conventional three-dimensional conformal radiotherapy may lead to excessive gastrointestinal and genitourinary toxicity. Image-guided radiotherapy (IGRT), by virtue of combining the steep dose gradient of intensity-modulated radiotherapy and daily pretreatment imaging, may allow for radiation dose escalation and decreased treatment morbidity. Reduced treatment time is feasible with hypo-fractionated IGRT and it may improve patient quality of life.

Feasibility of image-guided radiotherapy and concurrent chemotherapy for locally advanced nonsmall cell lung cancer.

A retrospective review of 32 patients with stage III nonsmall cell lung cancer who underwent chemoradiation with image-guided radiotherapy (IGRT) was recorded. Acute grade 3-4 hematologic and esophageal toxicities developed in 6 and 13 patients respectively. At a median follow-up of 14.5 months, only one patient developed grade 3 pneumonitis. The median survival was estimated to be 17 months. Five patients (15%) developed loco-regional recurrences, and 17 patients (53%) distant metastases. Grade 3-4 toxicities remained significant during chemoradiation with IGRT. However, the reduced rate of severe pneumonitis despite a high tumor dose is encouraging and needs to be investigated in future prospective studies.

Image-guided radiotherapy for cardiac sparing in patients with left-sided breast cancer.

Patients with left-sided breast cancer are at risk of cardiac toxicity because of cardiac irradiation during radiotherapy with the conventional 3-dimensional conformal radiotherapy technique. In addition, many patients may receive chemotherapy prior to radiation, which may damage the myocardium and may increase the potential for late cardiac complications. New radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) may decrease the risk of cardiac toxicity because of the steep dose gradient limiting the volume of the heart irradiated to a high dose. Image-guided radiotherapy (IGRT) is a new technique of IMRT delivery with daily imaging, which may further reduce excessive cardiac irradiation. Preliminary results of IGRT for cardiac sparing in patients with left-sided breast cancer are promising and need to be investigated in future prospective clinical studies.

Feasibility of tomotherapy-based image-guided radiotherapy for small cell lung cancer.

BACKGROUND: To assess the tolerance of patients with small cell lung cancer undergoing chemoradiation with tomotherapy-based image-guided radiotherapy (IGRT). MATERIALS AND METHODS: A retrospective review of the toxicity profile for nine patients with small cell lung cancer of the limited stage who underwent chemoradiation delivered with helical tomotherapy (HT) has been conducted. RESULTS: Acute grade 3-4 hematologic and esophagitis toxicities developed in two and three patients respectively. One patient developed a pulmonary embolism during radiotherapy. Seven patients had weight loss ranging from 0 to 30 pounds (median: 4 pounds). Three patients had treatment breaks ranging from 2 to 12 days. At a median follow-up of 11 months (range: 2-24 months), no patients developed any radiation related toxicities such as grade 3-4 pneumonitis or other long-term complications. The median survival was estimated to be 15 months. There were two local recurrences, three mediastinal recurrences, and six distant metastases. CONCLUSION: Grade 3-4 toxicities remained significant during chemoradiation when radiation was delivered with tomotherapy-based IGRT. However, the absence of grade 3-4 pneumonitis is promising and the use of HT needs to be investigated in future prospective studies.

Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer.

BACKGROUND: The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. METHODS: A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. RESULTS: At a median follow-up of 22 months (4-53 months), no patient developed retropharyngeal nodal recurrences. CONCLUSION: Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Altered glucose metabolism during chemoradiation for head and neck cancer.

UNLABELLED: Platinum-based chemotherapy has been reported to induce diabetes and hyperosmolar coma in nondiabetic patients. The aim of the present study was to determine whether the administration of chemoradiation for head and neck carcinoma alters glucose metabolism during and after treatment. PATIENTS AND METHODS: Weekly nonfasting serum glucose level was obtained during treatment of one hundred and six patients with locally advanced head and neck cancer who underwent chemoradiationt. RESULTS: For the 91 non-diabetic patients, mean serum glucose level measured 97.75 before and 102.1, 102, 104.1, 109.1, 109.7, 110.3, 109.8, 113.2, 107.7 and 104.3 mg/dl during weeks 1-10 of treatment respectively. Serum glucose level elevation reached statistical significance for weeks 5-8. CONCLUSION: Chemoradiation for head and neck cancer may produce severe glucose metabolism alteration during treatment.

Aspiration risk and postoperative radiation for head and neck cancer.

The aim of the study was to assess the aspiration risk following postoperative radiation for head and neck cancer. Thirty-seven patients had Modified Barium Swallow before and following treatment. Dysphagia severity was graded from 1 to 7. Before treatment there were sixteen grade 1, seventeen grade 2, three grade 3 and one grade 5. Following postoperative radiation, two patients had grade 1, eleven patients had grade 2, thirteen patients had grade 3, four patients had grade 4, four patients had grade 5, one patients had grade 6, and two patients had grade 7. Nineteen percent (7/37) of the patients developed aspiration (grade 5-7). Aspiration is life-threatening and may develop for all tumor sites and stages.

Long-term aspiration following treatment for head and neck cancer.

BACKGROUND: Dysphagia and aspiration are long-term complications with life-threatening consequences following treatment of head and neck cancer. We would like to assess the prevalence of aspiration in patients with long-term persistence of dysphagia (1 year or more) following treatment for head and neck cancer and to identify potential risk factors of aspiration. METHODS: Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. RESULTS: Between 1992 and 2004, 74 patients with dysphagia underwent MBS 12-152 months following treatment (median 29 months). There were 2 grade 1, 22 grade 3, 21 grade 4, 11 grade 5, 7 grade 6, and 11 grade 7 cases. Twenty-nine patients (39%) had long-term aspiration at a median follow-up of 25 months (range 12-82). Eighteen patients (24%) required permanent gastrostomy because of severe aspiration. Type of treatment and disease stage did not seem to influence long-term aspiration risk. CONCLUSION: Patients with long-term dysphagia after treatment for head and neck cancer are at risk of aspiration. MBS should be performed to identify these patients.

Dysphagia severity and aspiration following postoperative radiation for locally advanced oropharyngeal cancer.

UNLABELLED: The aim of the present study was to assess dysphagia severity following postoperative radiation for locally advanced oropharyngeal cancer. PATIENTS AND METHODS: Eighteen patients with oropharyngeal carcinoma had undergone postoperative radiation. There were eight base of tongue, eight tonsils, and two soft palate carcinomas. All the patients had undergone modified barium swallow (MBS) to assess the persistence of dysphagia (more than one month) post-treatment. All the patients were cancer-free at the time of the swallowing study. Dysphagia severity was graded as 1-7. RESULTS: At a median follow-up of 12 months, there were three grade 2, four grade 3, two grade 4, five grade 5, two grade 6, and two grade 7. Only three patients (17%) had normal swallow post-treatment. Six patients (33%) had mild to moderate dysphagia (grade 3-4). Nine patients (50%) developed aspiration (grade 5-7). Among the patients who developed aspiration, four (22%) required tube feeding for severe aspiration. CONCLUSION: Long-term (more than one year) dysphagia following postoperative radiation for oropharyngeal cancer may be symptomatic of permanent damage to the swallowing mechanism. Evaluation of patients who complain of persistence of dysphagia a year or more following treatment should include MBS, because of the increased risk of aspiration.

Prevalence of pharyngeal and esophageal stenosis following radiation for head and neck cancer.

OBJECTIVE: To evaluate the risk and outcome of pharyngoesophageal stenosis in patients who complained of dysphagia following radiation for head and neck cancer. DESIGN: Retrospective study. SETTING: Veterans Administration hospital. PATIENTS: Patients who complained of persistent dysphagia following radiation alone or combined with surgery or chemotherapy for head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. All patients had modified barium swallow (MBS) and an endoscopic examination for initial evaluation of their dysphagia. Traditional barium swallow was requested when there was a suspicion of pharyngoesophageal stenosis on MBS. RESULTS: Two hundred twenty-two patients underwent MBS for evaluation of dysphagia posttreatment. Traditional barium swallow confirmed the diagnosis of pharyngeal (n = 2) or esophageal (n = 14) stenosis in 16 patients. Eight patients had esophageal stenosis on endoscopic examination. All patients underwent dilatation for relief of their dysphagia. The number of dilatations performed was, respectively, one in 12 patients, two in 4 patients, three in 3 patients, four in 3 patients, five in one patient, and six in one patient. CONCLUSION: Pharyngeal and/or cervical esophageal stenosis may be the cause of dysphagia following radiation for head and neck cancer. Esophageal dilatations often offer temporary relief of the dysphagia.

Risk of aspiration following radiation for non-nasopharyngeal head and neck cancer.

OBJECTIVE: We assessed the rate of aspiration following radiation for non-nasopharyngeal head and neck cancer. DESIGN: Retrospective study. SETTING: Veterans Administration Hospital. PATIENTS: Thirty-three patients who underwent radiation for head and neck cancer. Modified barium swallow was performed prior to and following treatment to assess the persistence of dysphagia and aspiration risk. All patients were cancer free at the time of the swallowing study. Dysphagia severity was graded from 1 to 7. RESULTS: Preradiation baseline dysphagia was observed as follows: 10 grade 1, 14 grade 2, 9 grade 3, and 1 grade 4. Following radiation, at a median follow-up of 3 months, nine patients had grade 1, eight patients had grade 2, six patients had grade 3, two patients had grade 4, three patients had grade 5, two patients had grade 6, and three patients had grade 7. Overall, 24% (8 of 33) of the patients developed aspiration (grades 5-7). Fifteen percent (5 of 33) of the patients had severe aspiration (grades 6-7) requiring tube feedings. All patients who developed severe aspiration continued to require tube feedings more than 1 year following treatment completion. CONCLUSION: Aspiration is a significant source of morbidity following radiation for non-nasopharyngeal head and neck cancer. Aspiration may develop for all tumour stages or sites. Diagnostic studies such as modified barium swallow should be included in future prospective head and neck cancer studies to assess the prevalence of aspiration because of its often silent nature.

Effectiveness of the cough reflex in patients with aspiration following radiation for head and neck cancer.

The effectiveness of the cough reflex in patients who aspirated following radiation for head and neck cancer was evaluated in 89 patients (49 chemoradiation, 33 postoperative radiation, and 7 radiation alone). All patients had modified barium swallow because of dysphagia. The cough reflex was graded as present and effective, ineffective, intermittently effective, or absent. All patients were cancer-free at the time of the swallowing study. The cough reflex was present and effective in 46 patients (52%), ineffective in 17 patients (19%), and absent in 26 patients (29%) on initial investigation. Among the 43 patients who had ineffective or absent cough reflex, their treatment was chemoradiation (26), postoperative radiation (13), and radiation alone (4). In 30 patients who had sequential modified barium swallow, the cough reflex was constantly effective, ineffective, or intermittently effective in 12 (40%), 13 (43%), and 5 (17%) patients, respectively. The cough reflex was frequently ineffective or absent in patients who aspirated following radiation for head and neck cancer. Cough may also be intermittently ineffective to protect the airways following radiation.

Aspiration occurence during chemoradiation for head and neck cancer.

AIM: To assess the risk of developing aspiration during chemoradiation for head and neck cancer. PATIENTS AND METHODS: A retrospective review of 114 patients who underwent concurrent chemoradiation for locally advanced head and neck cancer was undertaken. Patients were determined as having aspiration if they had pneumonia on chest-X-ray (CXR) and/or had documented aspiration on the modified barium swallow (MBS) during their treatment. RESULTS: Fifteen patients (13%) developed aspiration during chemoradiation. Twelve patients (10%) had aspiration demonstrated on CXR alone (9 patients) or combined with MBS (3 patients). Three patients (3%) had aspiration on MBS alone. Three of the six patients with aspiration observed on MBS had normal swallowing on their pretreatment MBS. All 15 patients had severe mucositis and neutropenia at the time of the aspiration. Despite broad-spectrum antibiotics and supportive care, six patients (5%) died. CONCLUSION: Aspiration may develop during chemoradiation for head and neck cancer because of radiation-induced altered swallow.

Quality of life following chemoradiation and postoperative radiation for locally advanced head and neck cancer.

BACKGROUND: To evaluate the impact of chemoradiation and postoperative radiation on patients' quality of life (QOL) in a single institution. METHODS: A retrospective analysis of 101 patients who had treatment for locally advanced head and neck cancer in a single institution. Forty-seven patients had chemotherapy and radiation, 54 patients underwent postoperative radiation. QOL was assessed with the University of Washington (UW), and the Hospital Anxiety (HA) and Depression (HD) questionnaires. All patients were free of disease at the survey time. RESULTS: Mean and median UW scores were not different between the 2 groups: chemoradiation (65/67), postoperative radiation (62/63). Mean and median HA scores were 7.6/7 (chemoradiation), and 8.3/8 (postoperative radiation). Mean and median HD scores were 6.7/7 (chemoradiation), and 7.1/7 (postoperative radiation). Forty-four patients developed complications, with mean/median UW, HA, and HD scores of 55/55, 9.9/8, and 8.9/9, respectively. These scores were significantly different compared to the 57 patients without complications: 70/70 (p = 0.0001), 6.5/6 (p = 0.001), and 8.9/9 (p = 0.0001). CONCLUSION: There was no significant difference in QOL between chemoradiation and postoperative radiation in this retrospective study with a relatively short follow-up in the chemoradiation group. In addition, there were more patients with resectable disease in the postoperative group which may explain the lack of difference in QOL between the two groups. Patients who developed complications following treatment experienced lower QOL, more anxiety and depression. Our study raised the need to conduct a prospective randomized study to assess the real impact of chemoradiation and postoperative radiation on patients' QOL.

Concurrent chemoradiation for locally advanced oropharyngeal cancer.

PURPOSE: The aim of this study was to assess the survival, pattern of failure, morbidity, and prognostic factors of concurrent chemoradiation for locally advanced oropharyngeal cancer. MATERIALS AND METHODS: A retrospective survey of patients who underwent chemotherapy and radiation for locally advanced oropharyngeal carcinoma at the Veteran Affairs North Texas Health Care System, Dallas, Tex. RESULTS: Between December 1999 and September 2004, 48 patients with locally advanced oropharyngeal cancer underwent concurrent chemotherapy and radiation. At a median follow-up of 23 months, the 3- and 5-year survival for the whole group were, respectively, 52% and 41%. Seventeen patients (35%) developed recurrences. There were 12 (25%) locoregional failures (6 local failures alone and 6 local and regional failures). Distant metastases developed in 8 patients (5 alone, 3 associated with locoregional failures). Four patients (8%) developed second primaries. No difference was observed in survival between base of tongue and tonsillar carcinoma (P = .32). The 5-year survival for T1-T2 and T3-T4 tumors was, respectively, 84% and 27% (P = .01). No patient with T1-T2 tumors developed distant metastases (P = .04). Forty-five patients (94%) developed toxicity grade 3 to 4 (40 mucositis and 26 hematological). The median weight loss was 18 lb (range, 0-47 lb). Eight patients (16%) developed aspiration pneumonia during and after treatment. Five patients (10%) died of aspiration (2 during and 3 post treatment). Four patients (8%) developed esophageal strictures requiring repeated dilatations post treatment. Two patients had radionecrosis (1 soft tissue and 1 bone) requiring hyperbaric oxygen. Eighteen patients (37%) had prolonged tube feedings (>3 months) after treatments because of severe dysphagia or aspiration. CONCLUSION: Concurrent chemoradiation provided good locoregional control for locally advanced oropharyngeal carcinoma. Patients with small tumors (T1-T2) had excellent survival. The poor prognosis associated with large tumors may be due to the risk of developing distant metastases. Acute and late toxicities remained significant. Aspiration pneumonia and severe dysphagia were the most prevalent complications of the combined modality approach.

Impact of swallowing therapy on aspiration rate following treatment for locally advanced head and neck cancer.

This study examines the efficacy of swallowing therapy in cancer-free patients who developed aspiration following treatment for locally advanced head and neck cancer. The records of 41 patients who underwent swallowing therapy for aspiration were reviewed. All patients were cancer free at a median follow-up of 25 months (6-150 months). Their treatment were respectively chemoradiation (24), and postoperative radiation (17). All patients had two or more modified barium swallow (MBS). Dysphagia severity was graded from 1 to 7. Dysphagia grade was compared before and following swallowing therapy. Before swallowing therapy, there were 16 grade 5 (trace aspiration), and 25 grade 6-7 (severe aspiration). In the chemoradiation group, there were nine grade 5, five grade 6, and 10 grade 7. Corresponding numbers for the postoperative group were: seven grade 5, seven grade 6, and three grade 7. Following swallowing therapy, there were six grade 3, seven grade 4, 10 grade 5, six grade 6, and 12 grade 7. In the chemoradiation group, there were four grade 3, three grade 4, four grade 5, five grade 6, and eight grade 7. In the postoperative group, there were two grade 3, four grade 4, six grade 5, one grade 6, and four grade 7. Overall, 13 patients (32%) had improvement of their dysphagia severity. Seven of them were in the chemoradiation group (29%), and six (35%) were in the postoperative group. Among 25 patients who presented with grade 6-7 aspiration, only nine (36%) improved to grade 5 or less. Four of them (27%) were in the chemoradiation group, and five (29%) were in the postoperative group. Swallowing therapy is effective to improve dysphagia severity and reduce the need for tube feedings. However, a significant number of patients still suffered from chronic severe aspiration. New strategies must be devised to improve their outcome.

Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer.

OBJECTIVE: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. MATERIALS AND METHODS: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). RESULTS: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p=0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p=0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. CONCLUSION: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent.

Evolution of chronic dysphagia following treatment for head and neck cancer.

We would like to assess the evolution of chronic dysphagia (1 year or more) following treatment for head and neck cancer. Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. Each patient had at least 2 MBS. Severity of dysphagia was compared between the first and last MBS study to determine whether the swallowing dysfunction had returned to normal. Patients with complaint of dysphagia and normal MBS also underwent a regular barium swallow to assess the structural integrity of the pharynx and esophagus. Between 1996 and 2001, 25 patients with dysphagia underwent repeat MBS following treatment. Swallowing dysfunction did not return to normal in the majority of the patients. At a median time of 26 months following treatment (range 15-82 months), only two patient (8%) had normalization of the swallowing. The severity of dysphagia decreased in eight patients (32%), remained unchanged in 12 patients (48%), and worsened in five patients (20%). Eight patients (32%) still had aspiration problems at 12-83 months following treatment. Six patients (24%) required dilation because of pharyngeal stenosis. Three patients who required dilation had improvement of the dysphagia severity. Chronic dysphagia is a relentless process possibly due to excessive scarring. Patients with chronic dysphagia are at risk of malnutrition, and aspiration. Management of chronic dysphagia requires a team approach with nutritional support, psychological counseling, dilation, and tube feedings when indicated.