Context: Although it is well known that patients with advanced pancreatic cancer (PC) experience significant symptom burden, few strategies for effective symptom intervention are available for them.
Objectives: To investigate the efficacy of minocycline, an anti-inflammatory agent, for symptom reduction in patients with advanced PC.
Methods: We conducted Phase II, randomized, and placebo-controlled trial to obtain preliminary estimates of the effects on symptom reduction with 100 mg of minocycline or placebo given twice a day. Eligible patients had diagnosed advanced PC and were scheduled for standard chemotherapy. Patient-reported symptoms were measured weekly during the eight-week trial using the MD Anderson Symptom Inventory (MDASI) module in patients with gastrointestinal cancer. The primary outcome measure was the area under the curve values of the five most severe symptoms in the two arms.
Results: Of the 44 patients recruited, 31 (71%) were evaluable for the primary efficacy analysis, with 18 received minocycline and 13 placebo. Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were the most severe symptoms reported by both groups. No significant differences in area under the curve values over time between the study arms were found for the composite MDASI score or single-item scores of the five most severe MDASI items. No treatment-related deaths were reported, and no Grade 3–4 toxicities were observed.
Conclusion: Minocycline is safe for use in patients receiving treatment for PC. There is no observed symptom reduction with minocycline on the major symptom burden associated with advanced PC compared with placebo. Attrition because of rapid disease progression impacted the study significantly.
BACKGROUND: Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer. The secondary objectives were to describe the announcement of chemotherapy discontinuation and the time between chemotherapy discontinuation and death.
METHODS: This prospective multicenter French cohort included patients with advanced gastrointestinal cancer, for whom chemotherapy was discontinued between May 2016 and January 2018.
RESULTS: One hundred and fourteen patients were analyzed. The first cause of chemotherapy discontinuation was the impairment of general condition (asthenia, cachexia). Complications such as sepsis, jaundice or occlusion, were the second most frequent cause. Progression was observed at chemotherapy discontinuation in two-thirds of cases. The announcement of the chemotherapy discontinuation was made formally in 74% of cases, with a follow-up by a palliative care team initiated in 50% of cases. Sixty-nine percent of the patients received chemotherapy during the last three months of life and 26% during the last month. The median time between chemotherapy discontinuation and death was 65 days (IQR: 36.5-109): 44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.
CONCLUSION: Impairment of general condition was the major reason for chemotherapy discontinuation in patients with gastrointestinal cancers. Complications such as jaundice, sepsis or occlusion, were important reasons for discontinuation and could explain our shorter time between chemotherapy discontinuation and death, compared to other oncology sub-specialties.
BACKGROUND: Immune and targeted therapies continue to transform treatment outcomes for those with metastatic melanoma. However, the role of palliative care within this treatment paradigm is not well understood.
AIM: To explore bereaved carers' experiences of immune and targeted therapy treatment options towards end of life for patients with metastatic melanoma.
DESIGN: An interpretive, qualitative study using a social constructivist framework was utilised. Interviews were recorded, transcribed and analysed using grounded theory methods.
SETTING/PARTICIPANTS: Participants (n = 20) were bereaved carers of patients who had received some form of immune and/or targeted therapy at one of three Australian metropolitan melanoma treatment centres.
RESULTS: Carers struggled to reconcile the positive discourse around the success of immune and targeted therapies in achieving long-term disease control, and the underlying uncertainty in predicting individual responses to therapy. Expectations that immune and targeted therapies necessarily provide longer-term survival were evident. Difficulty in prognostication due to clinical uncertainty and a desire to maintain hope resulted in lack of preparedness for treatment failure and end of life.
CONCLUSION: Immune and targeted therapies have resulted in increased prognostic challenges. There is a need to engage, educate and support patients and carers to prepare and plan amid these challenges. Educational initiatives must focus on improving communication between patients, carers and clinicians; the differences between palliative and end-of-life care; and increased competency of clinicians in having goals-of-care discussions. Clinicians must recognise and communicate the benefit of collaborative palliative care to meet patient and family needs holistically and comprehensively.
Palliation of metastatic disease compromises a significant portion of radiation treatments in the United States. These patients present a unique challenge in resource-limited settings, as expeditious treatment is often required to prevent serious morbidity. In order to reduce the risk of infection with severe acute respiratory syndrome corona virus-2 and maximize the benefit to patients, we present evidence-based recommendations for radiation in patients with oncologic emergencies. Radiation oncologists with expertise in the treatment of metastatic disease at a high-volume comprehensive cancer center reviewed the available evidence and recommended best practices for the treatment of common oncologic emergencies, with attention to balancing the risk of infection with severe acute respiratory syndrome corona virus-2 and the potential morbidity of delaying treatment. Many prospective trials and national guidelines support the use of abbreviated courses of radiotherapy for patients with oncologic emergencies. As such, in the setting of the current coronavirus disease 2019 pandemic, the use of hypofractionated radiation therapy for patients requiring palliation for oncologic emergencies achieves desirable functional outcomes without compromising care.
Background: It remains unclear whether the end-of-life (EOL) treatment/environment impacts on survival after anticancer treatment in terminally ill women with ovarian carcinoma (OC).
Objective: The aim of this investigation was to clarify how long those women actually survived after their last anticancer treatments and their hallmarks.
Setting, Design, and Measurements: Between 2003 and 2011, 79 terminally ill women with OC were retrospectively analyzed as a single institutional study. Postcancer treatment survival (PCS), defined as the duration between the last date of the abovementioned “cancer treatment” and that of death from any cause, was analyzed on stratification by type of supportive care or where patients spend their EOL. Inverse probability of treatment weighting (IPTW)—adjusted Kaplan–Meier and Cox regression analyses were employed to compare PCS between the two groups.
Results: The median PCS of patients was 10.8 weeks. In the multivariable analysis, the performance status and EOL place retained their significance as independent prognostic factors of poorer PCS (performance status [2–3/0–1]: hazard ratio [HR] = 3.279 [95% confidence interval; CI 1.967–5.586; p < 0.0001], EOL place [hospital/home hospice]: HR = 0.574 [95% CI 0.355–0.913; p = 0.0188]). In the IPTW-adjusted cohort, the median PCS rates were 15.0 and 9.7 weeks in patients of home/hospice and hospital groups, respectively (p = 0.04). Also in the IPTW cohort, the EOL place retained its significance (IPTW-adjusted: HR [95% CI]: 1.548 [1.009–2.374], p = 0.045, multivariable adjusted with IPTW: HR [95% CI]: 1.670 [1.077–2.588], p = 0.022).
Conclusion: Our current data may be hypothesis generating; it is possible that the EOL environment is a crucial prognostic factor for survival after anticancer treatment.
Maman a un cancer, un lymphome, un gros pamplemousse qui l'empêche de respirer dans le poumon. On suit le parcours de soins, du diagnostic au traitement jusqu'à la guérison, à travers les yeux d'un petit garçon et de son papa.
Background: Lymphopenia during radiotherapy (RT) may have an adverse effect on treatment outcome. The aim of this study is to investigate associations between lymphopenia and RT parameters in patients with advanced lung cancer. Moreover, to investigate the prognostic role of lymphopenia, blood protein levels, and treatment and patient-related factors.
Material and Methods: Sixty-two advanced stage non-small cell lung cancer (NSCLC) patients were retrospectively analyzed. Blood counts were available prior to, during, and after RT (3Gyx10). For each patient, a thoracic volume of interest (VOI) -including thoracic soft tissue and trabecular bone- was obtained by applying a CT window of -500 to 1200 HU in the planning CT. Dose parameters from thoracic VOI and other regions including lungs and vertebrae were calculated. Association between risk of lymphopenia = G3 (lymphocytes at nadir according to CTCAE v4.0) and therapeutic parameters was investigated using Logistic regression. Relationships between overall survival (OS) and RT dose parameters, baseline blood counts and protein levels, and clinical factors were evaluated using Log-rank and Cox models.
Result: Mean thoracic RT dose (odds ratio [OR] 1.67; p = 0.04), baseline lymphocytes (OR 0.65; p = 0.01), and corticosteroids use (OR 6.07; p = 0.02) were significantly associated with increased risk of lymphopenia = G3 in multivariable analysis. Worse OS was associated with high mean thoracic RT dose, high CRP/Albumin, large tumor volume and corticosteroids use (p < 0.05, univariate analysis), but not with lymphopenia = G3. CRP/Albumin ratio > 0.12 (hazard ratio [HR] 2.28, p = 0.03) and corticosteroid use (HR 2.52, p = 0.01) were independently associated with worse OS.
Conclusion: High thoracic RT dose gave a higher risk of lymphopenia = G3; hence limiting dose volume to the thorax may be valuable in preventing severe lymphopenia for patients receiving palliative fractionated RT. Still, lymphopenia = G3 was not associated with worse OS. however, high baseline CRP/Albumin was associated with poorer OS and may carry important information as a prognostic factor of OS in advanced NSCLC receiving palliative RT.
Radiation therapy (RT) can effectively palliate a variety of symptoms in patients with metastatic cancer, using relatively low doses that infrequently cause major side effects. However, palliative radiation is often underutilized and sub-optimally implemented. In this study, we surveyed the Society of Palliative Radiation Oncology (SPRO) membership to identify barriers to appropriate referral for palliative RT that they encounter in their practice, and identify specific groups of physicians who radiation oncologists believed would benefit most from further education on when to refer patients. A total of 28 radiation oncologists responded to the survey with a response rate of 20.5%. On average, participants felt that referrals for palliative RT were inappropriately delayed 46.5% [standard deviation (STD) 20.2%] of the time. The most common barrier to referral for medical oncologists was thought to be potential interference with systemic therapy (33%); for primary care physicians and surgeons it was a lack of knowledge about the benefit (42%), and for palliative care physicians it was concern for patient convenience (25%). For brain metastases and spinal cord compression radiation oncology was felt to be part of the initial referral sequence more than 50% of the time, but less so for thoracic airway obstruction/bleeding (38%), esophageal obstruction (16%), or urinary obstruction/bleeding (8%), where another subspecialist was more often consulted first. Primary care, geriatric medicine, and emergency medicine were considered among the least knowledgeable specialties about palliative radiation. These hypothesis-generating findings can guide approaches to improve referral patterns for this important aspect of supportive care.
Background: Aggressive care at the end of life (EOL) is a persistent issue for patients with stage IV nonsmall cell lung cancer (NSCLC). We evaluated the use of concurrent care (CC) with hospice care and cancer-directed treatment simultaneously within the Veteran's Health Administration (VHA) and aggressive care at the EOL.
Objective: To determine whether VHA facility-level CC is associated with changes in aggressive care at the EOL.
Design/Setting: Veterans with stage IV NSCLC who died between 2006 and 2012 and received lung cancer care within the VHA.
Measurements: The primary outcome was aggressive care at EOL (i.e., hospital admissions, chemotherapy, and intensive care unit) within the last month of life. To compare aggressive care across VHA facilities, we used a random intercept multilevel logistic regression model to examine the association between facility-level CC within each study year (<10%, 10% to 19%, and =20%) and aggressive care at the EOL among the decedents as a binary outcome.
Results: In total, 18,371 veterans with NSCLC at 154 VHA facilities were identified. Facilities delivering CC for =20% of veterans (high CC) increased from 20.0% in 2006 to 43.2% in 2012 (p < 0.001). Overall, hospice care significantly increased and aggressive care at EOL decreased over the study period. However, facility-level CC adoption was not associated with any difference in aggressive care at EOL (adjusted odds ratio high CC vs. low CC: 0.91 [95% CI, 0.79 to 1.05], p = 0.21).
Conclusions: Although the VHA adoption of CC increased hospice use among patients with NSCLC, additional measures may be needed to decrease aggressive care at the EOL.
Background: Adults with impaired performance status (PS) often receive immune checkpoint inhibitors (ICIs) for advanced non–small cell lung cancer (NSCLC) despite limited efficacy data and unknown effects on end-of-life care.
Methods: This was a retrospective, single-site study of 237 patients with advanced NSCLC who initiated ICI treatment from 2015 to 2017. Cox regression was used to compare the overall survival (OS) of patients who had impaired PS (=2) at the start of ICI treatment with those who had PS 0 or 1 using Cox regression. Logistic regression was conducted to analyze the association between ICI use in the last 30 days of life and the use of end-of-life health care.
Results: The patient mean age at ICI initiation was 67 years (range, 37-91 years), and 35.4% of patients had PS =2. Most patients (80.8%) received ICI as second-line or later therapy. The median OS was 4.5 months in patients with PS =2 and 14.3 months in those with PS 0 or 1 (hazard ratio, 2.5; P < .0001). Among the patients who died (n = 184), 28.8% who had PS =2 received ICIs in their last 30 days of life compared with 10.8% of those who had PS 0 or 1 (P = .002). Receipt of ICI in the last 30 days of life was associated with decreased hospice referral (odds ratio, 0.29; P = .008) and increased in-hospital deaths (odds ratio, 6.8; P = .001), independent of PS.
Conclusions: Adults with advanced NSCLC and impaired PS experience significantly shorter survival after ICI treatment and receive ICIs near death more often than those with better PS. Receipt of an ICI near death was associated with lower hospice use and an increased risk of death in the hospital. These results underscore the need for high-quality communication about potential tradeoffs of ICIs, particularly among adults receiving ICIs as second-line or later therapy.
The optimal first-line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real-world use of first-line systemic treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first-line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010-2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab-containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab-containing regimen. The highest median OS was found in patients receiving a trastuzumab-containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83-1.02; TTF: HR 0.92, 95%CI 0.82-1.04) but significantly more grade 3-5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first-line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets.
Purpose: In recent years, radionuclides like 177Lu have been considered promising material for the creation of therapeutic radiopharmaceuticals. With the therapeutic use of radiopharmaceuticals, the absorbed doses per tumor may exceed 10 Gy. It is extremely important that doses absorbed by healthy organs and tissues do not exceed the threshold for the incidence of deterministic effects.
Materials and methods: The potential use of the radionuclide lutetium-177 for the palliative treatment of pain in bone metastases is analyzed. The radionuclide 177Lu is a beta-emitting nuclide with a maximal energy of 0.49 MeV and a half-life of 6.6 days (161 h). Two therapeutic agents were considered: methylene diphosphonate (MDP) and ethylenediamine tetramethylene phosphonic acid (EDTMP). Both drugs contain phosphorus compounds in their composition, which ensures high tropism in bone tissue. For both drugs, biokinetic models of 177Lu’s behavior in the human body are created. A number of studies have shown that the radiochemical stability of these drugs is about 99%: these calculations took into account the presence of a free 177Lu radionuclide in each solution. The absorbed doses in organs and tissues when using the radiopharmaceuticals 177Lu-MDP and 177Lu-EDTMP, as well as the currently used drugs 153Sm-EDTMP and 89SrCl2, are compared. In order to assess the risk of the patient’s exposure to a radiopharmaceutical, the absorbed doses are calculated for each organ where the radioactive label is mainly deposited: the kidneys, red bone marrow, liver and bone surface.
Results: The intensity of dose accumulation when using different drugs on the pathological focus is different. The drug 177Lu-MDP is faster than other drugs when it comes to the full realization of the expected dose; therefore, a therapeutic effect is achieved faster when it is used. The slowest absorbed dose accumulates when strontium chloride is used. To compare the effectiveness of preparations based on the 177Lu radionuclide, an analysis of the radiopharmaceuticals currently used for the palliative therapy of bone metastases (89SrCl2 and 153Sm-EDTMP) was performed. For 89Sr, the most vulnerable organs are the kidneys, red bone marrow and liver, while for 153Sm-EDTMP, red marrow bone is most vulnerable. For radiopharmaceuticals based on the 177Lu radionuclide, the most vulnerable organs are the kidneys, liver and red bone marrow. This proves the effectiveness of the 177Lu-MDP and 177Lu-EDTMP radiopharmaceuticals.
Conclusions: According to the results of the calculations, 177Lu-EDTMP and 177Lu-MDP demonstrate the best results for the palliative therapy of bone metastases.
A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50 mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39 Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14 months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30 Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15 Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis.
Anaplastic thyroid cancer (ATC) is an orphan disease with extremely poor prognosis. In particular, unresectable stage IVC ATC is extremely difficult to treat and is associated with a survival of only a few months, even when treated with irradiation and/or chemotherapy. In 2015, lenvatinib was approved for the treatment of ATC in Japan. The aim of the present study was to evaluate the efficacy of lenvatinib for stage IVC ATC. A total of 32 patients with pathologically confirmed stage IVC ATC who were treated at the Kanagawa Cancer Center between 2011 and 2018 were included in the present study, of whom 16 patients were treated with lenvatinib (L group). The remaining 16 patients received palliative therapy (P group), of whom 7 were treated with weekly paclitaxel, 2 received external radiation for tumor reduction 5 days per week until treatment completion, and 2 underwent tracheostomy to avoid the risk of asphyxiation. The survival curves of both groups were analyzed using the log-rank test. The median overall survival time of the L and P groups was 4.2 and 2.0 months, respectively. A significant survival benefit was observed in the L group compared with that in the P group (P=0.00298). A reduction in tumor size by =30% (clinical partial response) within 1 month after treatment was observed in 5 patients (31.3%) in the L group and in no patients in the P group. Therefore, lenvatinib treatment yielded a median survival benefit of ~2 months compared with palliative therapy in stage IVC ATC. However, although a reduction in tumor size by =30% was confirmed in 5 patients who received lenvatinib treatment, 2 of those patients succumbed to massive necrosis and bleeding. These results suggest that an appropriate lenvatinib dose reduction is necessary.
Background: The therapeutic landscape in medical oncology continues to expand significantly. Newer therapies, especially immunotherapy, offer the hope of profound and durable responses with more tolerable side effect profiles. Integrating this information into the decision making process is challenging for patients and oncologists. Systemic anticancer treatment within the last thirty days of life is a key quality of care indicator and is one parameter used in the assessment of aggressiveness of care.
Methods: A retrospective review of medical records of all patients previously treated at Goulburn Valley Health oncology department who died between 1 January 2015 and 30 June 2018 was conducted. Information collected related to patient demographics, diagnosis, treatment, and hospital care within the last 30 days of life. These results were presented to the cancer services meeting and a quality improvement intervention program was instituted. A second retrospective review of medical records of all patients who died between 1 July 2018 and 31 December 2018 was conducted in order to measure the effect of this intervention.
Results: The initial audit period comprised 440 patients. 120 patients (27%) received treatment within the last 30 days of life. The re-audit period comprised 75 patients. 19 patients (25%) received treatment within the last 30 days of life. Treatment rates of chemotherapy reduced after the intervention in contrast to treatment rates of immunotherapy which increased. A separate analysis calculated the rate of mortality within 30 days of chemotherapy from the total number of patients who received chemotherapy was initially 8% and 2% in the re-audit period. Treatment within the last 30 days of life was associated with higher use of aggressive care such as emergency department presentation, hospitalisation, ICU admission and late hospice referral. Palliative care referral rates improved after the intervention.
Conclusion: This audit demonstrated that a quality improvement intervention can impact quality of care indicators with reductions in the use of chemotherapy within the last 30 days of life. However, immunotherapy use increased which may be explained by increased access and a better risk benefit balance.
BACKGROUND: For most patients with oesophageal cancer worldwide, palliation of dysphagia is the goal which is most commonly achieved with self-expanding metal stents (SEMS). The aim of this study was to assess the profile and management of oesophageal cancer patients at Frere Hospital in the Eastern Cape, and compare this to a similar cohort from Groote Schuur Hospital (GSH) in the Western Cape Province.
METHOD: This study is a retrospective comparative cohort which reviewed all patients diagnosed with oesophageal cancer by the Frere Hospital and GSH endoscopy units from January to December 2015. Independent prospective electronic databases for the two hospitals were merged for comparative analysis.
RESULTS: During the study period, 346 and 108 patients were diagnosed with oesophageal cancer at Frere Hospital and GSH respectively. The rate of curative intended intervention was similarly low, with 3% of cases at Frere Hospital undergoing oesophagectomy or definitive radiotherapy as compared to 5% at GSH (p=0.48). In terms of palliation, significantly more patients received palliative oncological therapy at GSH as compared to Frere Hospital (21% vs 8%, p < 0.001). At Frere Hospital, 281 patients (81%) were treated primarily with serial dilatations. At GSH, 9 patients received a single dilatation, all as a bridge to radiotherapy or stenting. At Frere Hospital, 28 patients (8%) were stented, as compared to GHS where 69 patients (64%) were managed with a stent (p < 0.001).
CONCLUSION: This study shows significant differences in the oncological and endoscopic palliation of patients between the two institutions, highlighting a gross disparity in healthcare provision between them. The reasons for these disparities should be investigated and equipoise addressed by national health policy makers.
Background: Platinum-based chemotherapy is the standard of care as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC); however, the prognosis of patients with RM-NPC remains poor. The aim of this study was to evaluate the role of anti-epidermal growth factor receptor (anti-EGFR) antibody plus chemotherapy for RM-NPC.
Methods: RM-NPC patients who received first-line chemotherapy plus an anti-EGFR antibody were recruited from Sun Yat-Sen University Cancer Center between July 2007 and November 2017. Survival analyses were performed using the Kaplan-Meier method with a log-rank test. A Cox proportional hazards model was used for the multivariate analyses.
Results: A total of 203 patients were enrolled in the present study. The median follow-up time was 34.3 months (interquartile range: 19.7-66.5 months). The median progression-free survival (PFS) was 8.9 months (95% CI: 7.7-10.0 months) and the median overall survival (OS) was 29.1 months (95% CI: 23.5-34.6 months). The 1-, 3-, and 5-year PFS and OS rates were 35.5% and 79.6%, 15.2% and 42.5%, and 11.6% and 23.6%, respectively. The objective response rate (ORR) was 67.5% and the disease control rate (DCR) was 91.1%. The multivariate analysis identified the following prognostic factors for PFS: anti-EGFR agent (P = .010), recurrence/metastasis sequence (P = .016), KPS (P = .017), and combined chemotherapy regimen (P = .015). Independent risk factors for OS included age >43 years (P = .002), Karnofsky performance score =80 (P < .001), and higher level of baseline Epstein-Barr virus (EBV) DNA (P = .008). Leukopenia was the most common adverse event (AE) in this cohort (any grade, 84.2%; grades 3-4, 43.4%).
Conclusions: Anti-EGFR antibody plus chemotherapy achieved promising antitumor activity with a tolerable toxicity profile in RM-NPC. Thus, randomized clinical trials are warranted to compare the efficacy of chemotherapy with or without anti-EGFR antibody in these patients.
Futility in medicine has been defined as excessive medical intervention with very little prospect of altering the clinical outcome in a positive manner. If treatments fail to release our patients from the preoccupation with the illness and do not allow them to pursue their life goals, then perhaps that treatment is futile.
In the present study, the influence of purely palliative radiotherapy (pRT) on the outcomes of patients with advanced cancer undergoing immune checkpoint blockade was evaluated. Patients were stratified into three groups: Patients who had received pRT within 6 months prior to the initiation of immunotherapy (previous pRT); patients who received pRT during immunotherapy (concurrent pRT); and patients who did not receive RT prior to or during immunotherapy (no RT group), and these groups were compared. The median overall survival (mOS), median progression free survival (mPFS) and median time-to-treatment failure (mTTF) for the previous pRT group were significantly shorter compared with the no RT group (mOS, 3.6 vs. 12.1 months, respectively, P=0.0095; mPFS 1.8 vs. 5.4 months, respectively, P=0.0016; mTTF 1.8 vs. 5.7 months, respectively, P=0.0035). The concurrent pRT group had a longer mTTF compared with the previous pRT group and similar outcomes to the no RT group. In the previous pRT group, 26.9% of the patients experienced immune-related adverse events compared with 40.1% of patients in the no RT group. Despite the use of pRT during immunotherapy being considered safe, the results of the present study suggest that pRT has a negative effect on immune balance.
Introduction: Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Almost 2/3rds of patients have recurrent or metastatic (R/M) HNSCC. Treatment options for R/M HNSCC have evolved, with relatively little change in survival. Thus, it is imperative that management decisions must balance efficacy with toxicity and emphasize the importance of maintaining the patient's quality of life (QOL). Areas covered: We cover the various chemotherapeutic options available for R/M HNSCC including single agent chemotherapy, platinum-based doublets and triplet options. The role of cetuximab, immunotherapy and oral metronomic chemotherapy (OMCT) is also reviewed. We discuss the management of patients with platinum-refractory disease. Expert opinion: In all patients with R/M HNSCC, we recommend assessment of extent of disease, patient symptomatology, performance status, affordability and availability of logistic and social support. In patients with PD-L1 CPS =/> 20, pembrolizumab is an option. In patients with PD-L1 CPS < 20, pembrolizumab/cisplatin/5FU or cisplatin/5FU/cetuximab (EXTREME) may be considered based on affordability and availability. Options available that have a lower toxicity and can help to maintain the patient's QOL include; single agent chemotherapy, carboplatin/paclitaxel combination chemotherapy, sequential combination chemotherapy followed by cetuximab, replacing 5FU with docetaxel (TPEx regime) and OMCT.