Global disparities in cancer supportive care: An international survey.

BACKGROUND: The global cancer burden is rising, particularly in low- and middle-income countries (LMIC), highlighting a critical research gap in understanding disparities in supportive care access. To address this, the Multinational Association of Supportive Care in Cancer (MASCC) Health Disparities Committee initiated a global survey to investigate and delineate these disparities. This study aims to explore and compare supportive care access disparities between LMIC and High-Income Countries (HIC). METHODS: An online cross-sectional survey was conducted among active members of MASCC. Members, representing diverse healthcare professions received email invitations. The survey, available for 3 weeks, comprised sections covering (1) sociodemographic information; (2) clinical service/practice-related disparities in their region/nation; (3) population groups facing disparities within their region or country. Chi-squared or Fisher's exact test for cross-sectional analyses, and a multivariable logistic regression model was employed for statistical analysis. RESULTS: A total of 218 active members participated, with one-quarter (26.6%) from LMIC and 18.4% ethnic minorities, timely cancer care (43.7%) and timely supportive care (45.0%) emerged as the most pressing disparities globally. Notably, participants from LMIC underscored cancer drug affordability (56.4%) and supportive care guideline implementation (56.4%) as critical issues. Economically disadvantaged populations were noted as more likely to face disparities by both LMIC and HIC (non-US-based) respondents, while US-based respondents identified racial/ethnic minorities as facing more disparities. CONCLUSION: This global survey reveals significant disparities in cancer supportive care between LMIC and HIC, with a particular emphasis on medication affordability and guideline implementation in LMIC. Addressing these disparities requires targeted intervention, considering specific regional priorities.

Financial Toxicity in Cancer Supportive Care: An International Survey.

PURPOSE: The study aims to explore unmet social needs and sources of financial toxicities in patients as noted by health care professionals and researchers in cancer supportive care, shedding light on potential health disparities. METHODS: In this cross-sectional survey, we anonymously surveyed active members of the Multinational Association of Supportive Care in Cancer (MASCC). The survey, structured in three sections, included questions regarding the routine assessment of social needs during patient consultations, sociodemographic aspects, factors influencing financial toxicity (FT), perceived support for managing FT, and available/desirable resources. RESULTS: A total of 218 MASCC members were included, predominantly from high-income countries (HIC, 73.4%), with many age 41-60 years (56.5%) and female (56.9%). Drug/treatment cost and insurance coverage were the main sources for FT among the HIC, whereas participants from low-middle-income countries (LMIC) considered transportation cost, loss of employment because of cancer diagnosis, and unavailability of return-to-work services as the top three sources of FT. Respondents from LMIC (adjusted odds ratio [aOR], 3.01 [95% CI, 1.15 to 7.93]) and physicians (aOR, 2.67 [95% CI, 1.15 to 6.21]) were more likely to routinely assess financial coverages. Socioeconomic status was consistently ranked as one of the top three sources of financial toxicities by participants from LMIC (34%), HIC excluding the United States (38%), those who do not self-identify as racial/ethnic minority (36%), and physicians (40%). CONCLUSION: This global survey of health care professionals and researchers in HIC and LMIC revealed varying approaches to assessing financial coverage and social needs. Socioeconomic status emerged as a consistent concern across countries, affecting financial toxicities. The study highlights the need for tailored approaches and improved resource visibility while emphasizing clinicians' pivotal role in addressing financial aspects of cancer care.

An Innovation in Cancer Nursing Education Across Europe: A Pilot Evaluation.

The European Oncology Nursing Society (EONS) is a pan-European not for profit society involving approximately 28,000 cancer nurses from 32 countries in the region. The European College of Cancer Nursing (ECCN) exists under the umbrella of EONS and was established in 2020 with a strategic priority to develop, promote and deliver educational opportunities for nurses across Europe. ECCN introduced a pilot on-line education programme for 20 nurses in January 2023. This study evaluated participating nurses' views and experience of learning on the pilot programme. The study adopted a mixed method approach guided by the four levels of the Kirkpatrick theoretical framework. A dominant focus on qualitative data was used with supplementary quantitative data. The Standards for Reporting Qualitative Research (SRQR) was followed. Eleven nurses completed the pre-pilot online questionnaire (response rate 65%) and seven (n = 7) completed the post-pilot questionnaire (41% response rate). Five (n = 5) nurses participated in two focus group interviews. Data analysis resulted in the development of four overarching themes: A wider world of cancer nursing; Shapeless mentorship; Impact on Practice; Learning online and what now? On commencement of online education programmes, nurses value a structured timetable and support from nursing management to maximise engagement with the learning materials.

Equity, diversity, and inclusion in the Multinational Association for Supportive Care in Cancer: a global membership survey.

Equity, diversity, and inclusion (EDI) are essential for healthcare organizations since they allow for the development of programs and initiatives that bring together diverse perspectives and knowledge. Global multidisciplinary organizations, such as the Multinational Association for Supportive Care in Cancer (MASCC), need to understand the perspective of their members regarding EDI to identify opportunities to enhance diversity and inclusiveness and to better meet the needs of members from different backgrounds and resources. The MASCC Health Disparities Committee designed a survey to identify issues related to disparities faced by MASCC members when providing supportive care to patients with cancer and to examine the EDI landscape within the organization. Here, we report results related to EDI initiatives within the organization. Two-hundred and eighteen MASCC members responded to the survey (response rate 10.2%). The results indicated that respondents were generally satisfied with how MASCC manages leadership, membership, and organization-related EDI issues. Opportunities for improvement noted by respondents included developing strategies to foster a more diverse membership, improving communication regarding diversity in the organization, and increasing EDI content in educational sessions and publications. The results of this survey represent the first attempt at understanding how to improve EDI within MASCC and will be utilized to guide further initiatives and programs.

Patient perceptions of altering chemotherapy treatment due to peripheral neuropathy.

PURPOSE: Clinical practice guidelines recommend altering neurotoxic chemotherapy treatment in patients experiencing intolerable chemotherapy-induced peripheral neuropathy (CIPN). The primary objective of this survey was to understand patient's perspectives on altering neurotoxic chemotherapy treatment, including their perceptions of the benefits of preventing irreversible CIPN and the risks of reducing treatment efficacy. METHODS: A cross-sectional online survey was distributed via social networks to patients who were currently receiving or had previously received neurotoxic chemotherapy for cancer. Survey results were analyzed using descriptive statistics and qualitative analysis. RESULTS: Following data cleaning, 447 participants were included in the analysis. The median age was 57 years, 93% were white, and most were from the UK (53%) or USA (38%). Most participants who were currently or recently treated expected some CIPN symptom resolution (86%), but 45% of those who had completed treatment more than a year ago reported experiencing no symptom resolution. Participants reported that they would discontinue chemotherapy treatment for less severe CIPN if they knew their symptoms would be permanent than if symptoms would disappear after treatment. Most patients stated that the decision to alter chemotherapy or not was usually made collaboratively between the patient and their treating clinician (61%). The most common reason participants were reluctant to talk with their clinician about CIPN was fear that treatment would be altered. Participants noted a need for improved understanding of CIPN symptoms and their permanence, better patient education relating to CIPN prior to and after treatment, and greater clinician understanding and empathy around CIPN. CONCLUSIONS: This survey highlights the importance of shared decision-making, including a consideration of both the long-term benefits and risks of altering neurotoxic chemotherapy treatment due to CIPN. Additional work is needed to develop decision aids and other communication tools that can be used to improve shared decision making and help patients with cancer achieve their treatment goals.

Development of online cancer resources to support pre-registration nurses and allied health professionals.

Cancer rates are increasing, and more people are living with cancer and its consequences. Healthcare students will be caring for people affected by cancer in all clinical contexts. However, pre-registration programmes can include limited cancer education and not all students will have the opportunity for a clinical placement in a cancer setting. This can result in healthcare students feeling unprepared to care for people affected by cancer. To address this need, nine e-learning modules, collectively called The Foundations of Cancer Care, have been developed to support students' knowledge, understanding and confidence about cancer. This article outlines the development and peer review of The Foundations of Cancer Care. The resultant modules are freely available to all those with an Open Athens account or NHS or UK university email address via the NHS Learning Hub (https://learninghub.nhs.uk).

Patient and public involvement in research: Reflections and experiences of doctoral cancer nurse researchers in Europe.

PURPOSE: Early career researchers lack guidance about patient and public involvement (PPI). The overall aim of the study was to explore the knowledge and experiences of using PPI in research among doctoral students who are registered nurses. METHODS: This qualitative study included findings generated from reflective essays and focus groups involving ten registered cancer nurses who are undertaking doctoral research. The study has two stages of data collection. Participants initially wrote a reflective essay using a set of guiding questions to structure a response which was subsequently analysed. Two focus groups were then conducted to provide further insight into the themes identified in the reflective essays. Reflective thematic analysis was used to identify, name, and define the final themes. RESULTS: There were ten participants from seven countries and were at various stages of their doctoral study. Analysis of data from reflective essays (n = 10) and focus groups (n = 2) identified four themes namely, (a) evolving recognition and appreciation of PPI, (b) embracing PPI and impact on doctoral studies, (c) the influence of the research environment, and (d) the need to empower doctoral students to integrate PPI in their research journey. CONCLUSION: Participants reported differing experiences of PPI awareness showing disparity in guidance about PPI for junior researchers across Europe. We recommend provision of early PPI training for doctoral students to support and encourage involvement of patients and the public in their research. Opportunities for sharing PPI experiences to help improve PPI culture in research environments that support doctoral students should be explored.

A systematic review of behavioural and exercise interventions for the prevention and management of chemotherapy-induced peripheral neuropathy symptoms.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) can result in functional difficulties. Pharmacological interventions used to prevent CIPN either show low efficacy or lack evidence to support their use and to date, duloxetine remains the only recommended treatment for painful CIPN. Non-pharmacological interventions such as exercise and behavioural interventions for CIPN exist. PURPOSE: The aims were to (1) identify and appraise evidence on existing behavioural and exercise interventions focussed on preventing or managing CIPN symptoms, (2) describe psychological mechanisms of action by which interventions influenced CIPN symptoms, (3) determine the underpinning conceptual models that describe how an intervention may create behaviour change, (4) identify treatment components of each intervention and contextual factors, (5) determine the nature and extent of patient and clinician involvement in developing existing interventions and (6) summarise the relative efficacy or effectiveness of interventions to lessen CIPN symptoms and to improve quality of life, balance and muscle strength. METHODS: A systematic search of Ovid Medline, Cochrane Library, EMBASE, PsycINFO, Health Management Information Consortium, Global Health and CINAHL was performed to identify articles published between January 2000 to May 2020, followed by OpenGrey search and hand-searching of relevant journals. Studies that explored behavioural and/or exercise interventions designed to prevent or improve symptoms of CIPN in adults who had received or were receiving neurotoxic chemotherapy for any type of cancer, irrespective of when delivered within the cancer pathway were included. RESULTS: Nineteen randomised controlled trials and quasi-experimental studies which explored behavioural (n=6) and exercise (n=13) interventions were included. Four studies were rated as methodologically strong, ten were moderate and five were weak. Ten exercise and two behavioural interventions, including those that improved CIPN knowledge and self-management resources and facilitated symptom self-reporting, led to reduced CIPN symptoms during and/or after chemotherapy treatment. CONCLUSIONS: The extent of potential benefits from the interventions was difficult to judge, due to study limitations. Future interventions should incorporate a clear theoretical framework and involve patients and clinicians in the development process. IMPLICATIONS FOR CANCER SURVIVORS: Our findings show exercise interventions have beneficial effects on CIPN symptoms although higher quality research is warranted. Behavioural interventions that increase patient's CIPN knowledge, improve self-management capacity and enable timely access to symptom management led to reduced CIPN symptoms.

Filipino nurses' experiences and perceptions of the impact of climate change on healthcare delivery and cancer care in the Philippines: a qualitative exploratory survey.

Background: Because of its geographical location, the Philippines is vulnerable to the effects of climate change and almost all types of natural hazards such as typhoons, earthquakes, and volcanic eruptions. Cancer is one of the leading causes of death in the Philippines and is one of the major public health concerns. Little is known about how climate change affects cancer services in the Philippines. As the biggest workforce in most institutions, having awareness and knowledge about disaster preparedness and management among nurses can help in reducing the devastating effects of natural disasters on health services. Thus, it is important to understand Filipino nurses' experiences and perception of the impact of climate change on healthcare delivery and cancer care in the Philippines. Aim: This study explored Filipino nurses' experiences and perception of the impact of climate change on healthcare delivery and cancer care in the Philippines. Methods: This is a descriptive qualitative exploratory study. Participants were recruited using the snowballing technique and completed an online survey. Forty-six nurses who were working in Luzon, Philippines at the time of the data collection were included in the analysis. Data were analysed using thematic analysis. Findings: Three themes were identified, namely: (1) effects of climate change causing disruption and delay in provision of patient care, (2) impact of climate change on nurses and a deep sense of duty, and (3) perceived impact on patients with cancer. Conclusion: Our study findings contribute to the existing literature that focuses on the impact of climate change-related events such as typhoons and floods on healthcare services and nursing staff. Several areas of cancer care are also impacted, particularly delays in treatment such as chemotherapy. Despite the challenges, the nurses in our study demonstrated a deep sense of commitment in carrying out their roles.

Co-designing a behavioural intervention for reducing the impact of chemotherapy-induced peripheral neuropathy symptoms: An evidence- and theory-driven approach.

OBJECTIVE: This study aims to co-design an evidence- and theory-based behavioural intervention to reduce the impact of chemotherapy-induced peripheral neuropathy (CIPN) symptoms on patients' quality of life. METHODS: Guided by the Medical Research Council Framework for developing and evaluating complex interventions, our intervention development process was guided by (a) findings of systematic reviews, (b) inductive analysis of 39 h of observational fieldwork, 12 patient and 11 clinician interviews, (c) deductive analysis using the Common-Sense Model to develop a Self-Regulation Model of CIPN and (d) 17 patients and 18 clinicians co-designing the intervention. RESULTS: CIPN perception and coping behaviours were highlighted as processes to target when co-designing an intervention. The processes targeted in our intervention are CIPN perception and coping behaviours, namely, (a) self-monitoring of symptoms, (b) communicating and early reporting of symptoms to clinicians, (c) participating in making chemotherapy dose reduction decisions with their clinicians and (d) engaging in self-management and safety strategies to reduce impact of CIPN symptoms. To address these, a behavioural intervention was deemed suitable. CONCLUSION: We developed a self-regulation model of CIPN and a logic model for documenting the proposed mechanism of action of our co-designed behavioural intervention for reducing impact of CIPN symptoms.

Co-designing a cancer care intervention: reflections of participants and a doctoral researcher on roles and contributions.

BACKGROUND: Patient and Public Involvement is most usually framed in the context of designing, conducting and/or disseminating research. Participatory methods such as Experience-Based Co-Design (EBCD) further allow service users to directly engage in developing, testing and implementing interventions and services alongside healthcare staff. This paper aims to explore how participants in an EBCD project came-over time-to perceive their role and involvement in co-designing a cancer care intervention. METHODS: The findings are based on our reflections, a research diary, email correspondence and fieldnotes from co-design events. Co-design participants who attended most of the ten co-design events took part through written reflections or audio-recorded video calls. Ten reflective pieces were collected from clinicians (n = 4), PPI group members/patient participants (n = 4), a doctoral researcher (n = 1) and a visual illustrator (n = 1). Inductive data analysis of participant reflections was carried out using reflexive thematic analysis. Meeting fieldnotes, email correspondence and the researcher's diary were deductively analysed using the initial themes generated from this inductive analysis. RESULTS: Five main themes were identified: (1) changing perception of roles during the co-design process, (2) defining a 'co-designer', (3) engagement and ownership, (4) role of the research facilitator in maintaining momentum, and (5) perceived benefits of involvement. CONCLUSION: Our findings show the changing perceptions of roles and contributions among participants over time. Patients typically described their role as co-designers in terms simply of sharing their experiences. In contrast, clinicians perceived themselves as co-designers because they were working with patients who were actively involved in decision-making. Levels of engagement were affected by several factors such as time and facilitation, but most participants came to view themselves as co-owners of the intervention. Overall, participants perceived their involvement as a positive experience with clinicians also reporting wider positive impacts on their clinical practice.

Experience-Based Co-Design is a method for helping patients and clinicians work together to improve healthcare services. Studies of participant experiences in projects which use this method and how they perceive the co-designer role are rare. Our study explores how we­patients and clinicians­saw our role and participation as co-designers over time. Our findings are based on our written and verbal reflections of participating in a co-design project aimed at developing an information resource booklet and film for use in cancer care. We also analysed meeting records, email messages between participants and a reflective diary kept by the researcher who was coordinating the project. Our findings show that views of our roles and contributions as co-design participants changed over time. Patients tended to see themselves as 'co-designers' simply because they shared their experiences throughout the co-design process. In contrast, clinicians saw themselves as 'co-designers' because they were working together with patients and making decisions with them. Factors such as time demands, and the skill of the facilitator affected the commitment of participants to co-design activities. Most participants regard the ownership of the newly developed information resources as being shared. Overall, we viewed our participation in the co-design project as a positive experience with results that will benefit clinical practice.

A Systematic Review of Nutritional Lab Correlates with Chemotherapy Induced Peripheral Neuropathy.

Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy for which no prevention or cure exists. Cancer and cancer treatments can adversely affect nutritional status. Nutrition may play a role in development of CIPN, yet the relationship between nutrition and CIPN is not well understood. Common laboratory values measuring various aspects of nutrition (hemoglobin/hematocrit, vitamin B12, calcium, and magnesium) may be associated with CIPN. The aim of this systematic review is to evaluate the empirical evidence surrounding the relationship between laboratory measures of nutrition and CIPN among persons with cancer who received neurotoxic chemotherapy drugs. We conducted an extensive review of the literature to identify articles that evaluated relationships between laboratory measures of nutrition and CIPN. A total of eleven articles satisfied the inclusion/exclusion criteria. Participants in the studies had breast or colorectal cancer, lymphoma or multiple myeloma and were receiving a variety of neurotoxic drugs. Hemoglobin/hematocrit, vitamin D, albumin, and magnesium were associated with CIPN. The quality of the studies ranges from fair to good. Evidence suggests that low levels of the above-mentioned tests could be associated with CIPN but additional research is needed.

Clinician and patient experiences when providing and receiving information and support for managing chemotherapy-induced peripheral neuropathy: A qualitative multiple methods study.

OBJECTIVE: To improve patient experience of chemotherapy-induced peripheral neuropathy (CIPN), it is crucial to identify how patients develop their understanding and perception of CIPN. A wider understanding of the experiences of clinicians who provide CIPN information and support is also needed. This study explored clinician and patient experience of the provision of care, information and support for CIPN. METHODS: Data were collected between July and November 2019 using multiple qualitative methods. Non-participant observations were undertaken in colorectal and breast cancer clinics and at clinician stations, including the observation of chemotherapy consultations between patients and clinicians. Semi-structured interviews with people with cancer and clinicians were also conducted. Data were analysed using inductive reflexive thematic analysis. RESULTS: Three major themes emerged: (1) CIPN is a hidden chemotherapy side effect, (2) assessment and management of CIPN is disconnected and (3) patients and clinicians expect openness in CIPN symptom reporting, information provision and management. CONCLUSION: Findings show the need to address the lack of patients' overall familiarity with CIPN. Echoing earlier studies, our findings suggest that knowledge and understanding about CIPN among clinicians are limited or lacking. These insights from patient and clinicians' CIPN experiences can inform future interventions that may address the genuine needs of patients and enhance CIPN support.

Lived experiences and support needs of women who developed chemotherapy-induced peripheral neuropathy following treatment for breast and ovarian cancer.

OBJECTIVES: This study explored lived experiences of women who developed chemotherapy-induced peripheral neuropathy (CIPN) following treatment for breast and ovarian cancer. It also explored cancer survivors' perceptions of information and advice offered by clinicians about CIPN and for managing CIPN. METHODS: The study was advertised through cancer charity websites and social media accounts. Purposeful, convenience sampling was carried out using set eligibility criteria. Individuals with diagnosis of breast or ovarian cancer who experienced or are still experiencing CIPN were recruited. Fifteen semi-structured interviews were conducted. Data were analysed using interpretative phenomenological analysis (IPA). RESULTS: Similar to previous studies, participants used comparisons to describe their symptoms. Four main themes emerged from the analysis: (a) struggle to process CIPN information, (b) information and trust are key in the treatment decision-making process, (c) experience of symptom reporting and (d) challenges of managing symptoms. Findings suggest interventions to improve understanding of CIPN risk are needed in practice. CONCLUSION: A better and broader understanding of the patient experience of CIPN could pave the way for improved communication, assessment and management of symptoms. Results suggest the need for interventions to guide cancer survivors to recognise and report CIPN symptoms early and address the impact of CIPN symptoms in their lives.

A time to weep and a time to laugh: humour in the nurse-patient relationship in an adult cancer setting.

PURPOSE: The literature highlights the value of humour in health-care settings. Humour impacts on the physiological, psychosocial and cognitive well-being of a person. The diagnosis of cancer is extremely stressful, and treatments are difficult. Patients and nurses may use humour as a coping mechanism to contend with the stresses caused directly or indirectly by cancer. This study investigated the use of humour during interactions between patients and nurses in an adult cancer ward. METHODS: This study used a modified ethnographic methodology that included fieldwork participant observation and informal interviews (n=30 h) and formal interviews (n=10). In total, 9 nurses and 12 patients participated in participant observation. From these, five nurses and five patients were interviewed. Data were analysed using thematic analysis. RESULTS: Findings highlighted the importance of humour in the nurse-patient relationship. Patients consciously use humour during nurse-patient interactions in an attempt to help nurses cope with the stress they encounter in clinical practice. Patients perceive having a sense of humour as a positive nurse attribute. Nurses expressed concerns regarding compromising professionalism when using humour and felt the need for guidance from senior staff. Constant assessment and reflection help ensure humour is used appropriately in the adult health-care setting. CONCLUSION: The benefits of humour are recognised by both adult cancer patients and nurses. A deeper understanding of patient and nurse perceptions of the use of humour can inform strategies for its therapeutic use in the clinical setting.

Humour in adult cancer care: a concept analysis.

AIMS: To report an analysis of the concept of humour in adult cancer care. BACKGROUND: Humour is a form of communication which is present in the adult cancer setting. Numerous studies show the multi-dimensional value of humour in cancer care. A clear conceptual understanding, however, of what it represents is lacking. DESIGN: Walker and Avant's framework was used to guide this concept analysis. DATA SOURCES: Literature searches included bibliographic databases, internet, and manual searches. REVIEW METHODS: Literature published from 1990 to the present was reviewed. Thematic analysis was carried out to identify critical attributes and antecedents. RESULTS: Based on the analysis, a definition of humour in adult cancer nursing is proposed. Humour is a subjective emotional response, resulting from the recognition and expression of incongruities of a comic, absurd and impulsive situation, remark, character, or action, which enhances feelings of closeness or togetherness when shared in the context of trust between the patient and nurse and may be used as a coping mechanism in a stressful situation such as the adult cancer care setting. CONCLUSION: The analysis provides an understanding of the concept of humour in the adult cancer setting and includes a theoretical illustration of its critical attributes. This concept analysis provides a forum for discussion with reference to the use of humour in adult cancer nursing care. Further exploration is recommended to determine the meaning of humour and its nature across different care settings.

Chemotherapy in the community: the importance of patient assessment.

The use of chemotherapy has expanded considerably in the UK in recent years, with an increase of around 60% in the amount of chemotherapy delivered over a four-year period (National Chemotherapy Advisory Group (NCAG), 2009). This has led to an increased demand for the delivery of chemotherapy, putting pressure on existing cancer services. Combined with the current political agenda which aims to improve the convenience and experience of health for patients' this has prompted the reorganisation of chemotherapy services, with a movement away from the delivery of chemotherapy in dedicated cancer centres to community-based models of care. This article discusses the implications of these changes for community nurses with regard to their role in the assessment of patients receiving chemotherapy.

Dose-escalated intensity-modulated radiotherapy is feasible and may improve locoregional control and laryngeal preservation in laryngo-hypopharyngeal cancers.

PURPOSE: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). METHODS AND MATERIALS: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. RESULTS: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. CONCLUSIONS: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study.

Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck.

PURPOSE: This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN). EXPERIMENTAL DESIGN: Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m(2) on days 1, 22, and 43) and dose-escalating (10(6), 10(6), 10(6), 10(6) pfu/mL for cohort 1; 10(6), 10(7), 10(7), 10(7) for cohort 2; 10(6), 10(8), 10(8), 10(8) for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored. RESULTS: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months). CONCLUSIONS: JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 10(6), 10(8), 10(8), 10(8). Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN.