Radiotherapy for head and neck cancer in nonagenarian patients: a possible cornerstone?

In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or more and with head and neck cancer (HNC). We made one of the first retrospective study of the feasibility and safety of radiotherapy in this population with HNC. Records of radiotherapy coming from four health facilities were studied to include all nonagenarian patients with HNC in the last 10 years and who received radiation therapy. We analyzed patient characteristics and primary cancers, as well as objective of the treatment (curative or palliative), efficacy and toxicity. Twenty patients receiving radiotherapy were identified; mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 40 and 60 % of cases, respectively. The most common primary tumors were tumors of the salivary glands (30 % of cases), oral cavity tumors (25 % of cases) and thyroid tumors (15 % of cases). Median total prescribed dose was 47.5 Gy (12-70 Gy). Median number of delivered fractions was 18.5 (2-35 fractions). All patients received intensive supportive care during radiotherapy. Toxicities were mild to moderate. Radiotherapy could not be completed for four patients (20 % of cases). One patient developed grade 1-2 delayed toxicities. At the last follow-up, only four patients (20 % of cases) were alive. Cancer was cause of death in most cases. Radiotherapy may be performed for the nonagenarians with HNC. The total dose and fractionation must be adjusted to optimize the tolerance. However, the prognosis remains very poor, cancer being the main cause of death. Research of geriatric vulnerabilities prior to any treatment, in the context of a comprehensive geriatric assessment, is still recommended to select patients for radiotherapy.

Management of Merkel cell carcinoma with emphasis on small primary tumors--a case series and review of the current literature.

A case series of Merkel cell carcinoma (MCC) is reported here and illustrates some of the current controversies in clinical management of this disease. From 1988-2007, 145 cases (74 men and 71 women) were analyzed. These were combined with other cases in the literature, hence the total number of patients was 433. Nodal metastases occurred clinically at presentation in 9/105 (9%) patients with primary tumor size <1 cm. The rate of nodal metastases is too high to obviate sentinel node biopsies even for these small tumors. For the 87 patients with intermediate tumor size (>1 - <2 cm), nodal metastases occurred clinically in 11 of 87 patients (13%) at presentation and 23 of 87 patients (26%) during follow-up. Distant metastases occurred in 20 of 87 patients (23%) only at follow-up. The risks of nodal and distant failures for tumors of intermediate sizes were sufficient to be classified as high-risk for clinical study purposes.

Reappraisal of clinical outcome in adult medulloblastomas with emphasis on patterns of relapse.

BACKGROUND: Clinical outcome and prognostic factors were assessed in adult medulloblastoma patients, with emphasis on patterns of relapse. PATIENTS AND METHODS: Records of 36 consecutive adult patients with medulloblastoma were reviewed. Patients were classified into 2 prognostic groups according to the extent of disease and quality of surgical excision based on the early postoperative magnetic resonance imaging (MRI) findings. Standard-risk (SR) patients (n = 11) received postoperative craniospinal radiation therapy (RT) only, 36 Gy, 1.8 Gy per daily fraction, with a 18 Gy boost to the posterior cerebral fossa (PCF). High-risk (HR) patients (n = 25) received additional adjuvant chemotherapy. RESULTS: With a median follow-up of 46 months (range 5-155), 19 patients experienced tumour relapse. Sites of relapse(s) included tumour bed in 6 patients, resulting in a PCF control of 83.4%. Three-year overall survival (OS) and progression-free survival (PFS) were 67.3% and 57.4%, respectively. The comparison of the HR and SR populations demonstrated significant differences in OS (p = 0.005) and PFS (p = 0.001). Quality of surgical excision and extent of disease beyond the PCF were predictive factors for OS (p = 0.04, p = 0.001, respectively) and PFS (p = 0.004, and p = 0.02, respectively). CONCLUSION: The quality of resection was a significant prognostic factor, suggesting that surgery should be as extensive as possible. Systematic postoperative MRI allowed accurate selection of SR patients for whom RT alone was enough to obtain high local control. Every effort should be made to avoid RT disruption. Increased delay led to worse outcome.

Efficacy and tolerance of thoracic radiotherapy in the oldest old patients: A case series.

BACKGROUND: There are only scarce data on the management of nonagenarians with lung cancer, and more particularly on the place of radiation therapy. The aim of the present study was to retrospectively evaluate the efficacy and tolerance of radiotherapy (RT) in nonagenarians with thoracic cancer. PATIENTS AND METHODS: Records from RT departments from four institutions were reviewed to identify patients 90 years old of age and older undergoing RT over the past decade for thoracic cancer and more particularly lung cancer. Tumors' characteristics as well as treatment specificities and its intent were examined. RESULTS: Thirteen patients receiving RT courses were identified, mean age 91.9 years. Treatment was given with curative and palliative intent in 15.4% and 84.6%, respectively. The median total prescribed dose was 30 Gy (4-70). The median number of fractions was equal to 10 (1-35). The median dose received for each fraction was 3 Gy (1.7-7). RT could not be completed in 2 patients (15.4%). At last follow-up, 11 patients (76.9%) were deceased, cancer being the cause of death for 90% of them. Most toxicities were grade 1 or 2. Two patients (15.4% of cases) have developed grade 2 toxicity during treatment. One patient (7.7% of cases) experienced an acute grade 3 toxicity. CONCLUSION: The study shows that RT for thoracic cancer is feasible in nonagenarians. Although the definitive benefit of RT could not be addressed here, hypofractionated therapy allowed a certain measure of control with acceptable side effects.

Radiotherapy for gynecologic cancer in nonagenarian patients: a framework for new paradigms.

No consensus exists regarding the role of radiotherapy in the management of gynecologic cancer in nonagenarian patients. We retrospectively reviewed the outcomes of 19 consecutive nonagenarian patients with gynecologic cancer (6 endometrial cancers, 6 cervical cancers, 4 vulvar cancers, and 3 vaginal cancers) who were treated with radiotherapy. Radiotherapy was performed mainly in a palliative setting (n = 12; 63.2%), with a median dose of 45 Gy (range, 6-76 Gy). Infrequent major acute or late toxicities were reported. Among 19 patients, 9 (47.4%) experienced tumor progression, 5 (26.3%) experienced complete response, 2 (10.5%) experienced stable disease and/or partial response. At last follow-up, 12 patients (63.2%) had died; most deaths (n = 9) occurred because of the cancer. These results suggest that radiotherapy is feasible in the treatment of nonagenarian patients with gynecologic cancer.

Male Breast Cancer Prognostic Factors Versus Female Counterparts with Propensity Scores and Matched-Pair Analysis.

OBJECTIVE: To assess the effect of prognostic factors and their impact on survival in male and female breast cancer. METHODS: Medical records for men and women diagnosed with breast cancer referred to the cancer center for treatment were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with and without hormone and radiation therapy (RT), survival, and recurrence were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female differences in prognostic factors. Male breast cancer (MBC) and female breast cancer (FBC) were matched according to propensity scores and survival compared using Cox regression. RESULTS: From 1963-2006, there were 75 MBC and 1,313 FBC totaling 1,388 breast cancers. The median age of the cohort was 53 (range: 23-90) years. Median follow-up was 90 (range: 0.4-339) months. Prognostic factors of patients were balanced among the groups after adjusting for propensity scores. A Cox model adjusting for propensity scores showed that overall survival (OS) (HR= 2.52 (1.65, 3.86), P<0.001) and distant disease recurrence-free survival (DDRFS) (HR= 2.39 (0.75, 3.04), P=0.003) were significantly different for MBC and FBC. Analyses that stratified by propensity score quintiles had similar findings: OS HR=2.41 (1.67, 3.47), P<0.001); DDRFS HR=2.89 (1.81, 4.60), P<0.001). When MBC and FBC were matched (1:3) by propensity scores, differences between MBC and FBC were again observed in OS (HR=1.94, 95%CI:1.18-3.19, P=0.009) and DDRFS (HR=2.79, 95%CI:1.36-5.75, P=0.005) with MBC at a higher risk of death and  disease recurrence compared to FBC . CONCLUSION: This large series showed that MBC and FBC survivals are not similar, with MBC having a worse outcome. The finding of this study needs confirmation from a complete prospective database.

Hypofractionated radiation therapy for treatment of bladder carcinoma in patients aged 90 years and more: A new paradigm to be explored?

INTRODUCTION: There are only scarce data on the optimal management of patients who present with a bladder carcinoma and who are aged 90 years and older. PATIENTS AND METHODS: We retrospectively reviewed records from radiotherapy departments from two university hospitals, two private centers and one public center to identify patients who underwent radiotherapy for bladder cancer over the past decade and who were aged 90 years or older. From 2003 to 2013, 14 patients aged 90 years or older receiving RT for bladder malignant tumors were identified. RESULTS: Mean age was 92.7 years. Ten patients (71 %) had a general health status altered (PS 2-3) at the beginning of RT. A total of 14 RT courses were delivered, including six treatments (43 %) with curative intent and eight treatments (57 %) with palliative intent. Palliative intent mainly encompassed hemostatic RT (36 %). At last follow-up, two patients (14 %) experienced complete response, one patient (7 %) experienced partial response, three patients (21 %) had their disease stable, and three patients (21 %) experienced tumor progression, of whom two patients with the progression of symptoms. There was no reported high-grade acute local toxicity in 14 patients (100 %). One patient experienced delayed grade 2 toxicity with pain and lower urinary tract symptoms. At last follow-up, seven patients (50 %) were deceased. Cancer was the cause of death for five patients. CONCLUSION: Hypofractionated radiotherapy remains feasible for nonagenarians with bladder cancer. Further investigations including analysis of geriatric comorbidities and impact of treatments on quality of life should be conducted.

Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients.

PURPOSE: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. METHODS AND MATERIALS: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. RESULTS: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10(-6)). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (-77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. CONCLUSION: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.

Portrait, treatment choices and management of breast cancer in nonagenarians: an ongoing challenge.

There are only scarce data on the management of nonagenarians with breast cancer, and more particularly on the place of radiation therapy (RT). We report a retrospective study on patients aged 90 years old or older, with breast cancer, receiving RT. Records from RT departments from five institutions were reviewed to identify patients 90 years old of age and older undergoing RT over past decade for breast cancer. Tumors' characteristics were examined, as well treatment specificities and treatment intent. 44 patients receiving RT courses were identified, mean age 92 years. Treatment was given with curative and palliative intent in 72.7% and 27.3% respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery, and tumor stage. Median total prescribed dose was 40 Gy (23-66). Hypo fractionation was used in 77%. Most toxicities were mild to moderate. RT could not be completed in 1 patient (2.3%). No long-term toxicity was reported. Among 31 patients analyzable for effectiveness, 24 patients (77.4%) had their diseased controlled until last follow-up, including 17 patients (54.8%) experiencing complete response. At last follow-up, 4 patients (12.9%) were deceased, cancer being cause of death for two of them. The study shows that breast/chest RT is feasible in nonagenarians. Although the definitive benefit of RT could not be addressed here, hypofractionated therapy allowed a good local control with acceptable side effects.

Feasibility of radiation therapy in patients 90years of age and older: a French multicentre analysis.

BACKGROUND: There are only scarce data on the management of patients aged 90years or older with cancer, and more particularly on the place of radiation therapy (RT). We report the first large study on patients (pts) aged 90years or older receiving RT. METHODS AND MATERIALS: Records from RT departments from five institutions were reviewed to identify pts 90years of age and older who underwent RT for various malignant tumours treated between 2003 and 2012. Tumours' characteristics were examined, as well as treatment specificities and treatment intent. RESULTS: 308 pts receiving 318 RT courses were identified, mean age was 93.2years (standard deviation 2.8). Treatment was given with curative and palliative intent in 44% and 56%, respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery and tumour stage. Median total prescribed dose was 36Gy (4-76Gy). Hypofractionation and split course were used in 88% and 7.3%, respectively. Most toxicities were mild to moderate. RT could not be completed in 23 pts (7.5%). No long-term toxicity was reported. Median overall survival was 22.9months (95CI: 15.5-42.7months). Cancer was the cause of death in 8.7% and 46% of pts treated with curative and palliative intent, respectively. CONCLUSION: This study shows that RT is feasible for patients aged 90years or more. PS, place of life and tumour stage were factors of the therapeutic decision. There is no reason to withdraw pts with good general health condition from potentially curative RT, provided that careful attention is paid to factors of toxicity and to geriatric vulnerabilities.

General management of nonagenarian patients: a review of the literature.

The number of nonagenarian people in the world is steadily growing. This phenomenon will increase in future years: in 2050, world population prospects estimate 71.16 million people aged 90 years or older. The two main causes of death among people aged 85 years or more in Europe in 2003 were cardiovascular and cerebrovascular diseases and cancers. However, the elderly are often excluded from clinical trials; they are underrepresented in clinical registries and especially nonagenarians. Care (medical, surgical, oncology) of these very elderly is currently insufficiently based on scientific recommendations. For the physician, the choice to treat or not to treat very elderly patients (for fear of side effects) is difficult. Oncology is particularly affected by this problem. Here we review these different fields of internal medicine management of nonagenarian patients with a special focus on oncology and on comprehensive geriatric assessment as a base for all care decision taking.

Prophylactic cranial irradiation for patients with limited-stage small-cell lung cancer with response to chemoradiation.

BACKGROUND: Previous clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. PATIENTS AND METHODS: The Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). RESULTS: There were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively). CONCLUSIONS: Patients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation.

Prognostic factors for male breast cancer: similarity to female counterparts.

AIM: To assess whether prognostic factors in male (MBC) and female (FBC) breast cancer have similar impact on survival. PATIENTS AND METHODS: Charts for men and women diagnosed with breast cancer referred to the London Regional Cancer Program (LRCP) were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with/without hormone and radiation therapy (RT), overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed. Survival estimates were obtained using the Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female differences in prognostic factors. RESULTS: From 1963-2006 there were 75 cases of MBC and 1,313 of FBC totaling in 1,388 breast cancer cases. The median age of the cohort was 53 (range=23-90) years. The median follow-up was 90 (range=0.4-339) months. Of the prognostic factors considered, nodal status had a significant Cox regression interaction. For OS, p=0.001 with hazard ratios of 0.83 (95% confidence interval CI=0.42-1.64) and 2.88 (95% CI=2.36-3.52) for males and females, respectively. For CSS p=0.041 with hazard ratios of 1.22 (95% CI=0.45-3.27) and 3.52 (95% CI=2.76-4.48) for males and females, respectively. For node-positive cases, distant disease recurrence-free survival was worse for MBC (log rank, p<0.001). CONCLUSION: This large series showed that the nodal status influences survival differently in MBC and FBC. The findings of this study need confirmation from a more complete prospective database and further investigations on improving high-risk node-positive MBC management are warranted.

Validation of robust tools to measure sialorrhea in amyotrophic lateral sclerosis: a study in a large French cohort.

There is an unmet need for validated tools to measure sialorrhea in amyotrophic lateral sclerosis, especially to evaluate treatments. We assessed the inter-/intra-rate reviewer reliability of two scales: the Oral Secretion Scale (OSS), specifically developed for ALS patients, and the Sialorrhea Scoring Scale (SSS), initially developed for Parkinson's disease patients. Sialorrhea was rated in 69 ALS consecutive patients by four evaluators: two neurologists, one nurse and one speech therapist. Inter-rater reliability was evaluated by the light kappa coefficient and intra-rater reliability by the weighted kappa coefficient. We also compared patients' and caregivers' answers. Results demonstrated that the two scales present a high inter-/intra-rater reliability: weighted kappas were 0.85 for both scales and light kappas 0.89 for the OSS and 0.88 for the SSS. Both scales also showed a good intra-profession reliability (OSS kappa = 0.84; SSS kappa = 0.79) and agreement between patients' and caregivers' answers. The SSS showed a higher responsiveness compared to OSS. In conclusion, both Oral Secretion Scale and Sialorrhea Scoring Scale are reliable tools to measure sialorrhea in ALS patients. Because of the wide range of salivation degrees, SSS may be more sensitive as a tool to evaluate treatments in patients with severe hypersialorrhea.

Role of conservative (palliative) care-only in the management of advanced malignant pleural mesothelioma.

Despite new aggressive therapeutical options for advanced malignant pleural mesothelioma (MPM), benefits to survival remain limited. Moreover, deleterious effects of high-dose chemotherapy and aggressive surgery are well-known. Outcomes of untreated patients are usually not reported, and whether a treatment can be delayed or avoided is still an open question. We discuss here two clinical cases and with conservative (palliative) management alone for advanced MPM [corrected].

Focal 3D conformal high-dose hypofractionated radiotherapy for brain metastases.

The optimal management of patients with few brain metastases is complex. On one hand, stereotactic radiation therapy is a keystone of treatment but is only applicable to highly selected patients fulfilling specific criteria who have access to an adequate radiation unit. On the other, whole-brain radiation therapy may improve survival, but deleterious effects on neurocognitive functions are well known. It has, however, been reported that selected subgroups of patients may benefit from focal dose escalation to brain metastases to prolong survival and the time to intracranial disease progression. Here, we discuss a clinical case to consider the interest of a focal high-dose hypofractionated radiation delivered through a conventional linear accelerator on a large brain metastasis for a patient with metastatic melanoma excluded for stereotactic radiotherapy.

Whole brain radiotherapy: prognostic factors and results of a radiation boost delivered through a conventional linear accelerator.

PURPOSE: Assess prognostic factors for overall survival and the potential benefit of a boost in patients treated with whole brain radiation therapy (WBRT). METHODS AND MATERIALS: From 2002 to 2006, a retrospective analysis was made from 250 unselected consecutive patients with secondary brain metastases from lung cancer, breast cancer and melanoma. Eighteen patients received surgery and were excluded from analysis. Four potential prognostic factors have been studied: primary tumor type, gender, number of metastases and improvement of neurological symptoms after radiation therapy. A subgroup analysis was performed to determine whether an additional boost could potentially improve outcome in patients who presented with less than three metastases, performance status <2, and no surgical resection of their metastasis. RESULTS: Average follow-up was 10.3 months. Median overall survival was 5.6 months and survival rates at 1 and 2 years were 22.7% and 10%, respectively. Age less than 65 (p<0.01), neurological improvement after WBRT (p<0.01), and presence of less than three metastases were significant factors for overall survival in multivariate analysis. When focusing on the selected subgroup (120 assessable patients), median overall survival was 4.0 months in patients with no radiation boost, versus 8.9 months in patients with radiation boost (p=0.0024). CONCLUSIONS: Survival and prognostic factors were similar to those found in the literature. Boost delivered after WBRT by a conventional particle accelerator could provide a benefit in selected patients, especially for centers that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment.

Merkel cell carcinoma of skin-current controversies and recommendations.

The review covers the current recommendations for Merkel cell carcinoma (MCC), with detailed discussion of many controversies. The 2010 AJCC staging system is more in-line with other skin malignancies although more complicated to use. The changes in staging system over time make comparison of studies difficult. A wide excision with margins of 2.5-3 cm is generally recommended. Even for primary