Combined chemotherapy and radiation therapy for head and neck malignancies: quality of life issues

BACKGROUND: The standard of care for locally advanced head and neck carcinoma usually has been surgery followed by radiation therapy. Patient survival using this approach has been reported to be poor. The disfiguration resulting from surgery and the long-term morbidity of postoperative radiation often results in considerable distress. Concurrent chemotherapy and radiation was introduced to improve outcome. Excellent local control and survival results often have been reported in Phase II and Phase III studies. The acute toxicity of combined chemotherapy and radiation is significant. However, organ preservation may improve quality of life. This review article summarizes the findings from published series of surgery, postoperative radiation, radiation therapy alone, and chemoradiation with regard to quality of life issues for patients with locally advanced head and neck carcinoma. METHODS: A literature search was used to identify quality-of-life studies of postoperative radiation, radiation therapy alone, and chemoradiation in patients with locally advanced head and neck carcinoma. Factors affecting long-term quality-of-life issues in each treatment modality were identified, compared, and evaluated. RESULTS: Speech disorder, dysphagia, pain, and depression were found to be the common side effects affecting quality of life regardless of the treatment modality. Xerostomia is the major complication affecting patients undergoing radiation or chemoradiation. CONCLUSIONS: Acute side effects of combined chemotherapy and radiation therapy usually were found to resolve after treatment. Long-term morbidity is substantial because of xerostomia and severe dysphagia. However, preliminary studies suggest that because of organ preservation, patients may achieve a better quality of life after chemoradiation compared with the conventional use of surgery and postoperative radiation.     

Prognosis, clinical outcomes and quality of life issues in cutaneous T-cell lymphoma

Although the need for a specific QOL index for MF/SS has been recognized, little work has been done in this area. QOL instruments should address general health concepts, as well as specific issues that are relevant to patients who have MF/SS; a combination of two instruments may be appropriate. Confirming the validity, reliability, and responsiveness to change of a combination of QOL instruments, such as SKINDEX-29 and FACT-G, in patients who have MF/SS will be relevant. For patients who have MF/SS, focusing our efforts on improving the disease and their QOL should translate into improvements that are meaningful to them. Thus, our goal should be to incorporate the findings of QOL research into practice and use the results to guide our practices, as they relate to therapy. Some important considerations are: We must be explicit about what will be done with the information that is obtained about an individual's QOL. We should consider what additional knowledge QOL measures provide that we could not otherwise have. We should be ready for unexpected results, as exemplified by instances where aggressive therapy could result in improved QOL. Although challenges exist in moving forward QOL research in CTCL, the words of wisdom of Tannock bring the concept of QOL into perspective: "When cure remains elusive, it is time to start treating the patient, not just the tumor." A final consideration is that we should not forget the dimension of spirituality, which is especially relevant to patients who have advanced MF/SS. Spirituality is characterized by the capacity to seek purpose and meaning, to have faith, to love, to forgive, and to see beyond current circumstances. Spirituality enables a person to rise above suffering. Unfortunately, research on spirituality is scarce, in part, because of the difficulty in assessing spiritual suffering. Nevertheless, physicians who are caring for patients who have advanced MF/SS should acknowledge the spiritual dimension as an integral component of the dying process.     

Curative-intent radiation therapy in anal carcinoma: quality of life and sphincter function.

In 22 colostomy-free survivors of curative-intent radiation therapy or chemoradiation for anal carcinoma, measurement of the Gastrointestinal Quality of Life Index (GIQLI) revealed a mean 114 of a maximum 144 points, as compared to 121 in healthy volunteers (n = 150) and 113 in patients with benign anorectal diseases (n = 325). Sixteen patients underwent anorectal manometry to determine anal sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), rectal compliance (RC) and relaxation of the internal anal sphincter (RIAS). SL, RP and MSP were significantly lower in anal carcinoma patients than in healthy volunteers. Complete continence was detected in 56% of patients.     

Potential impact of improvements in radiation therapy on quality of life and survival

The NCI goal for the U.S. is to reduce the cancer mortality rate to one-half by the year 2000. Part of this improvement will be due to use of state of art treatment on a population wide basis and in addition, major improvements in efficacy of treatment. More effective radiation therapy will result in fewer local failures, increased survival, reduced treatment associated morbidity, and less frequent complications of treatment. The latter two aspects are very important to quality of life. If radiation combined with other modalities (e.g., sensitizers) were to become of greatly enhanced efficacy, then the number of patients requiring cystectomy, abdominal perineal resection, pneumonectomy, amputation, etc., would come down. The beneficial consequence would be fewer patients subjected to permanent ileostomy, colostomy, etc. The increase in survival if local failure were eliminated was estimated to be the decrease in local failure less the same loss in the new local controls due to DM as obtained in the local control patients after conventional treatment. For all sites, patients experience higher survival rates if they do not have local failure. For those sites where loss due to metastasis is not high, more effective local therapy would result in numerically impressive gains in survival.     

Examining quality of life issues in relation to endocrine therapy for breast cancer

With the development of highly effective, well-tolerated third-generation aromatase inhibitors (AIs), these drugs will probably play an increasingly important role in all phases of breast cancer treatment. As a result, the impact of such hormonal agents on patients' quality of life bears rigorous investigation. In a randomized, multicenter, single-blind cross-over study, the AIs letrozole and anastrozole were evaluated for quality of life, toxicity, and patient preference. A total of 72 patients were enrolled and were treated with each drug for a 4-week period, with a 1-week drug-free washout period before cross-over to the alternate agent. Assessments included the FACT-ES, toxicity, and patient preference. The FACT-ES is a validated questionnaire designed to measure quality of life of women with breast cancer who are being treated with endocrine therapies. Letrozole was superior to anastrozole with respect to both quality of life and toxicity evaluations. In addition, at the conclusion of the trial, reduced nausea, hot flashes, and abdominal discomfort caused almost twice as many patients to prefer to continue with letrozole therapy than with anastrozole. Data from this recent trial indicate that letrozole is better tolerated and provides better quality of life than anastrozole for women with metastatic breast cancer.     

Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy

Of 77 patients with supratentorial Grades I and II astrocytoma diagnosed from January 1975 to December 1984, 66 were treated with postoperative radiation therapy. The patients received a tumor dose of 5000 to 5500 cGy in 180 cGy fractions, five fractions per week, over 5.5 to 6 weeks. Overall actuarial survival at 2, 5, and 10 years was 71%, 55%, and 43%, respectively. Progression-free survival at 2, 5, and 10 years was 69%, 50%, and 39%, respectively. Survival for patients receiving postoperative radiation therapy in the range of 4500 to 5900 cGy was 78% and 66% at 2 and 5 years, respectively. Quality of life was determined at two points in time: 1 to 2 years postoperatively, and at last follow-up (2-12 years postoperatively). The occurrence of mental retardation was specifically addressed in long-term survivors, and was observed in 50% of children. Overall, however, 80% of short-term survivors and 67% of long-term survivors were intellectually and physically intact, without major neurologic deficit. Specific prognostic factors were assessed by multivariate analysis. Improved survival was observed with young patients, females, normal preoperative mental status, surgical resection (versus biopsy alone), involvement of only one lobe with tumor, and a history of preoperative seizures. A weighted prognostic factor score derived from these observations permits a clinically useful assessment of risk for individual patients.     

Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy

BackgroundLymphoma patients undergoing therapy must cope with the side-effects of the disease itself, therapy and associated immobility. Peripheral neuropathy (PNP), loss of balance control and weakness not only diminishes patients' quality of life (QOL), it can also affect planning and the dosage of therapy. Exercise may enable patients to reverse these declines, improving their performance level and QOL.Patients and methodsWe carried out a randomized, controlled trial, assigning 61 lymphoma patients either to a control group (CG; N = 31) or to a 36-week intervention (IG; N = 30), consisting of sensorimotor-, endurance- and strength training twice a week. Primary end point was QOL; secondary end points included movement coordination, endurance, strength and therapy-induced side-effects.ResultsIntergroup comparison revealed improved QOL- (Δ_T1–T0; P = 0.03) and PNP-related deep sensitivity in the IG: 87.5% were able to reduce the symptom, compared with 0% in the CG (P < 0.001). Significant differences in the change of balance control could be found between the groups, with the IG improving while the CG steadily declined (monopedal static Δ_T3–T0; P = 0.03; dynamic Δ_T3–T0; P = 0.007; perturbed mono-Δ_T3–T0; P = 0.009 and bipedal Δ_T3–T0; P = 0.006), failed attempts (monopedal static Δ_T3–T0; P = 0.02, dynamic Δ_T3–T0; P < 0.001and perturbed Δ_T3–T0; P = 0.006) and improved time to regain balance (Δ_T3–T0; P = 0.04). Moreover, the change in the aerobic performance level (Δ_T3–T0; P = 0.05) and additional amount of exercise carried out per week [metabolic equivalent (MET); P = 0.02] differed significantly across groups.ConclusionsExercise, especially sensorimotor training, is a feasible and promising method to support cancer patients during therapy. It improves patients QOL, reduces restrictions from side-effects such as PNP and improves patients' balance control, physical performance level and mobility.German Clinical Trials Register numberDRKS00003894.     

Executive functioning,academic skills,and quality of life in pediatric patients with brain tumors post-proton radiation therapy

Radiation therapy (RT) is integral in the treatment of pediatric brain tumors; however, photon RT (XRT) often results in intellectual decline, executive functioning (EF) deficits, academic underachievement/failure, and lower health-related quality of life (HRQoL). Proton RT (PRT) provides more targeted therapy, minimizing damage to the developing brain, yet few studies have examined its neuropsychological effects. This study investigated the role of EF in academic skills and HRQoL in a sample of children treated with PRT. A mediation model was proposed in which academic skills mediated relations between aspects of EF and school-based HRQoL (sHRQoL). Sixty-five children (x?_age?=?12.4; 43.9% male) treated with PRT completed follow-up neuropsychological testing as part of routine care. Measures included assessment of intellectual functioning, EF, attention, and academic skills (reading, math, spelling). Parents reported on children’s EF and attention problems. sHRQoL was assessed via child self-report. Children who underwent PRT demonstrated relatively intact intelligence, academics, attention, EF, and sHRQoL, but were at risk for reduced processing speed. Poorer working memory and processing speed were related to lower sHRQoL. Better EF and faster processing speed were associated with better academic skills, which were linked to higher sHRQoL. Better working memory was associated with better math performance, which was linked to higher sHRQoL; this relationship did not hold for reading or spelling. Results highlight the importance of EF skills in academic performance and sHRQoL, and the need for routine screening of EF deficits and proactive supports. Supports may include cognitive rehabilitation and in-class accommodations. Overall, results compare favorably to XRT outcomes reported in the literature.     

Assessment of secondary radiation and radiation protection in laser-driven proton therapy

This work is a feasibility study of a radiation treatment unit with laser-driven protons based on a state-of-the-art energy selection system employing four dipole magnets in a compact shielded beamline. The secondary radiation emitted from the beamline and its energy selection system and the resulting effective dose to the patient are assessed. Further, it is evaluated whether or not such a compact system could be operated in a conventional treatment vault for clinical linear accelerators under the constraint of not exceeding the effective dose limit of 1 mSv per year to the general public outside the treatment room. The Monte Carlo code Geant4 is employed to simulate the secondary radiation generated while irradiating a hypothetical tumor. The secondary radiation inevitably generated inside the patient is taken into account as well, serving as a lower limit. The results show that the secondary radiation emanating from the shielded compact therapy system would pose a serious secondary dose contamination to the patient. This is due to the broad energy spectrum and in particular the angular distribution of the laser-driven protons, which make the investigated beamline together with the employed energy selection system quite inefficient. The secondary radiation also cannot be sufficiently absorbed in a conventional linear accelerator treatment vault to enable a clinical operation. A promising result, however, is the fact that the secondary radiation generated in the patient alone could be very well shielded by a regular treatment vault, allowing the application of more than 100 fractions of 2 Gy per day with protons. It is thus theoretically possible to treat patients with protons in such treatment vaults. Nevertheless, the results show that there is a clear need for alternative more efficient energy selection solutions for laser-driven protons.     

Overview of antibody therapy in B-cell non-Hodgkin's lymphoma

The main treatment modalities for lymphoma in the past decade have been radiation therapy and chemotherapy. Recently, molecular engineering provided humanized antibodies with promising clinical activity, and rituximab is the first commercially available antibody. This anti-CD20 monoclonal antibody (MoAb) showed little toxicity and demonstrated excellent clinical activity. Given as a single agent, it induces a high-response rate even in pretreated low-grade non-Hodgkin's lymphoma, the effect being higher if administered for a prolonged period of time. Its action is synergistic with chemotherapy, and combination treatment could improve survival in patients with aggressive lymphomas. Rituximab also demonstrated the ability to clear tumor cells from the circulation, allowing for an in vivo purging effect in the setting of peripheral stem cell collection and transplantation. Still, a number of issues related to its use need to be addressed, such as optimal dose and schedule and the situations in which rituximab should be given as a single agent or in addition to chemotherapy or other drugs, such as other MoAbs or interferons. We also need to understand when rituximab should be used in first-line treatment, with which type of chemotherapy the combination is most cost-effective, and patient population that will benefit most from this antibody treatment.     

Hyperfractionated radiation therapy in Burkitt's lymphoma: a reconsideration aspect

Burkitt's lymphoma (BL) is an aggressive non‐Hodgkin's B‐cell lymphoma with an extremely short doubling time that often presents in extra nodal sites or as an acute leukaemia. Nowadays, with the rapid response to chemotherapy and the diffuse nature of BL, there is no established role for radiation therapy (RT) even in localized disease. Regarding the relapsed/refractory BL, the treatment recommendations remain undefined. We present a 56‐year‐old woman, diagnosed with BL refractory to 6 cycles of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), who had disease progression on R‐DHAP (rituximab, dexamethasone, high dose cytarabine and cisplatin) with intrathecal methotrexate, then a partial response on RICE (rituximab, ifosfamide, carboplatin and etoposide). Patient received high dose chemotherapy and autologous haematopoietic stem cell transplantation. Then, she was treated with hyperfractionated involved‐field RT regimen. Currently, the patient remains disease free for around 2 years after remission. We acknowledge that RT is not a standard treatment of BL, especially in patients who attain complete response (CR) after first‐line multi‐agent chemotherapy or even in those who have a CR after second‐line chemotherapy pre‐transplant. Yet, the use of a superfractionated regimen of consolidative radiation could be justified in the treatment of recurrent/refractory localized BL who do not achieve a CR even with second‐line salvage chemotherapy. Radiation therapy in this context, given that it is a well‐tolerated treatment, is a modality worthy of being re‐considered in relapsed/refractory BL. Copyright © 2016 John Wiley & Sons, Ltd.     

Role of radiation therapy in localized non-Hodgkin's lymphoma

Relapse occurs in 50% of patients receiving radiation for clinical stage (C.S.) I and II nodal and extranodal non-Hodgkin's lymphoma (N.H.L.). Prior to the introduction of intensive chemotherapy those failing primary control with irradiation and most of those who relapsed died of their disease with a resultant overall mortality of 50%. An analysis of Princess Margaret Hospital results with radiation for C.S. I and II N.H.L. between January 1967 and December 1978 revealed that tumour bulk, age, stage and histology were of independent prognostic significance. It was possible to group patients using combinations of these attributes so that each group encompassed only patients with similar outcomes. Such prognostic groups were identified separately within the low grade and the intermediate plus high grade categories of the Working Formulation. Patients with a high probability of cure with radiation were so defined. Also those patients in whom chemotherapy would be optimal initial therapy were also defined. Such patients were in the intermediate plus high grade histology groups. Thirty percent of all patients with low grade histology lymphoma had an actuarial survival of 83%, and relapse-free rate of 63% at 10 years. By implication, approximately 20% of all patients with these histologies seen at the Princess Margaret Hospital for the same time period achieved prolonged relapse-free survival by localized therapy. This is at variance with the implications of staging from studies where laparotomy and multiple bone marrow biopsies have been used. Such aggressive staging procedures suggest truly localised disease in only 5-6% of patients with low grade lymphoma. A significant relationship between radiation dose and disease control was demonstrated only for patients with intermediate and high grade lymphoma of medium or large bulk. A minimum tumour dose of 30 Gy was required for optimal local control with radiation.     

AIDS-related non-Hodgkin's lymphoma: the outcome and efficacy of radiation therapy

The records of all 16 patients with AIDS-related lymphoma treated with radiation therapy at our institutions were reviewed. All patients were male with a median age of 32 years, and all but one had biopsy proven high-grade NHL. Eleven had lymphoma involving the central nervous system and five had lymphoma involving other sites. Seven of the 11 patients with CNS involvement had primary CNS lymphoma. All patients were treated with megavoltage X rays to doses ranging from 1050 cGy in 1 1/2 weeks to 5037 cGy in 6 weeks. Of those patients with CNS lymphoma, only one responded completely and four responded partially to irradiation. All patients died within a range of 0.2 to 5.3 months (median survival = 2.2 months) from starting radiation therapy. In contrast, 3 of 5 patients (60%) with NHL outside the CNS responded completely and 1 responded partially to involved-field irradiation. These patients survived a median of 12.6 months with one achieving long-term lymphoma-free survival at 40 months. This long-term survivor presented with Stage IE lymphoma as his only manifestation of AIDS. We conclude that AIDS-related lymphomas respond less favorably to radiation therapy than lymphomas in non-immunosuppressed patients. Furthermore, CNS lymphomatous involvement is an ominous occurrence in the AIDS patient. In our experience, cranial irradiation failed to provide significant palliation or survival prolongation in this group of patients. Instead, long-term survival is possible in AIDS patients with limited NHL outside the CNS, and it is in these patients that combination chemotherapy plus involved-field radiation therapy may play a curative role.     

Global and health-related quality of life after intensity-modulated radiation therapy for head and neck cancer

This study aims to evaluate the current literature regarding the effects of conventional radiation therapy (CRT) versus intensity-modulated radiation therapy (IMRT) on global quality of life (QoL) among patients treated for head and neck cancer. A PubMed literature review was performed. Only articles comparing global QoL scores in head and neck cancer patients treated with CRT versus IMRT were included. Studies were scrutinized for methodology, level of evidence and limitations. Outcomes were evaluated for external validity, level of evidence and applicability. Between 2005 and 2012, 14 eligible studies (six prospective, two randomized controlled trials) were identified. Although all presented data comment on the advantages of IMRT, differences in study design made comparisons difficult. The vast majority of these were also limited by relatively small sample sizes and heterogeneity with respect to patient and treatment-related characteristics. Although more robust evidence is needed in the future, the published data reasonably support the benefits of IMRT as compared with CRT (either 2D or 3D) in improving QoL, beginning at approximately 3–6 months post-treatment, and possibly potentiating with time up to 2 and 3 years.     

Social comparisons and quality of life following a prostate cancer diagnosis

Purpose: The objective was to explore the relationships among cognitive appraisals of prostate cancer (challenge, threat, and harm/loss), social comparisons, and quality of life in men previously diagnosed. Design, Sample, & Methods: Men who had participated in prostate cancer support groups completed a cross-sectional questionnaire (N = 189). Multivariable linear regression was used to evaluate social comparisons as mediators of quality of life while controlling for uncertainty and optimism. Findings: Positive and negative social comparisons were parallel mediators of the relationships between challenge or threat appraisals and quality of life, while only negative social comparisons mediated the relationship between harm/loss appraisals and quality of life. Conclusions: These findings demonstrate the importance of social comparisons in accounting for the effect of cognitive appraisals of prostate cancer on quality of life among men in support groups. Implications for Psychosocial Providers: Interventions to improve quality of life could address reduction of maladaptive comparisons, a strategy that could be tailored based on the patient's appraisal of prostate cancer.     

Individual quality of life in patients with leukaemia and lymphoma

With increasingly sophisticated chemotherapy regimes being prescribed the quality of life of cancer patients has become a key outcome measure. Little has been reported concerning the experience of patients with haematological malignancy receiving chemotherapy. The objective of this study was to evaluate the clinical usefulness of a novel quality of life measure-the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) in a sample of patients with either leukaemia or lymphoma. Fifty-one patients from the haematology clinic and in-patient unit at The Royal Devon and Exeter Hospital completed the SEIQoL-DW; in addition, each patient completed the Hospital Anxiety and Depression Scale (HADS) and a ten item questionnaire covering aspects of their treatment and satisfaction with information provided. The practical application of the SEIQoL-DW is described and two patients quality of life profiles are illustrated for comparison. The relationship between quality of life, satisfaction with information provided and psychological distress as measured by the HADS is discussed.     

Anxiety, depression and quality of life of cancer patients undergoing radiation therapy: a cross-sectional study in a community hospital outpatient centre

The purpose of the present study is to determine the impact of illness characteristics and psychopathological comorbidity on the quality of life (QoL) of radio-oncological patients in health-related and individual dimensions. Sixty-three of 93 eligible patients (40 women and 23 men) were included in the study during their radiation therapy visit to an outpatient centre annexed to a community hospital in Southern Bavaria, Germany. In a semi-structured interview, we elicited individually relevant life domains rated by the patients according to the 'Schedule for the Evaluation of Individual Quality of Life - Direct Weighting'. In addition, the participants completed the 'European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30' and the 'Hospital Anxiety and Depression Scale'. We also assessed the demand for psychotherapy and utilization of psycho-oncological services. In total, 9.5% of the examined patients suffer from clinically relevant anxiety and/or depression [total Hospital Anxiety and Depression Scale (HADS) score >19]. There was a weak positive correlation between Karnofsky's Performance Status and QoL. Anxiety and depression were significantly correlated with impaired QoL, especially with impaired individual QoL. There was no association between psychopathological comorbidity and the requirement for psycho-oncological support. Conversely, patients who report difficulties in accepting help had a significantly lower QoL. Psychopathological comorbidity has a considerable influence on QoL of patients undergoing radiotherapy. Measuring the individual QoL appears as an adapted needs assessment and helps the psychotherapist in focusing on the patient's problems and desires. Furthermore, the patient's QoL is a main target in providing or planning mental health care in non-university oncological services.