Active treatment given in the last weeks of life: poor quality cancer care or justifiable behavior?

PURPOSE: Chemotherapy near the end of life is frequently considered as an indicator of inappropriate aggressiveness. We were interested in revising our prescribing habits and in analyzing the reasons for offering active treatment to patients with advanced cancer. METHODS: We examined the electronic medical records of all the cancer patients died in the Italian Region of Valle d'Aosta in a 1-year period and extracted all the available clinical data. From the 350 deceased patients, we selected the 141 to whom active treatment had been given during the natural history of their disease. RESULTS: Among the patients undergoing any active treatment, the median number of days from the last administration to death was 75. Thirty-seven patients (26.2 %) had their last treatment administration during the 4 weeks before death and 20 (14.2 %) during the last 2 weeks. Fourteen patients (9.9 %) started treatment during the last 4 weeks. When the patients undergoing treatment in the last 4 weeks of life were compared with those subject to earlier withdrawal, only age and pretreatment were statistically significantly different. Most of the treatment choices were considered appropriate, and earlier treatment withdrawal could have been advised only in a minority of the cases. CONCLUSIONS: Our data were at the lower range when compared with the available literature. Uncertainties in prognostication and the possibility of response to treatment can justify chemotherapy prescriptions in selected cases. We suggest that the focus should move to the provision of adequate and timely supportive care.

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy.

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027). Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation.

Doege-Potter syndrome by malignant solitary fibrous tumor of the liver: A case report and review of literature.

BACKGROUND: Solitary fibrous tumor of the liver (SFTL) is a rare occurrence with a low number of cases reported in literature. SFTL is usually benign but, 10%-20% cases are reported to be malignant with a tendency to metastasize. The majority of malignant SFTL cases are associated with a paraneoplastic hypoglycaemia defined as Doege-Potter syndrome. Surgery is the best therapeutic treatment, however, long- life follow-up is recommended. CASE SUMMARY: A 74-year-old man, was admitted to the emergency department after a syncopal episode with detection of hypoglycaemia resistant to medical treatment. The computed tomography revealed a solid mass measuring 15 cm of the left liver. An open left hepatectomy was performed with complete resection of tumor. Histopathological analyses confirmed a malignant SFTL. CONCLUSION: Large series with long-term follow-up have not been published neither have clinical trials been undertaken. Consequently, the methodical long-term follow-up of surgically treated SFTLs is strongly recommended.

Syndrome of inappropriate anti-diuretic hormone secretion in cancer patients: results of the first multicenter Italian study.

BACKGROUND: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting. METHODS: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015. Data on clinical-pathological characteristics, anticancer therapies, hyponatremia, and related treatments were statistically analyzed. RESULTS: The majority were lung cancer patients (73%) with metastatic disease at the onset of hyponatremia (83%). A total of 76 patients (84%) were hospitalized because of SIADH and less than half (41%) received tolvaptan for SIADH treatment. The duration of hospitalization was significantly longer in patients who did not receive tolvaptan and in those who do not reach sodium normalization during hospitalization. Patients who experienced a second episode of hyponatremia following tolvaptan dose modification/discontinuation presented a significantly lower serum sodium value at the time of hospitalization and minimum sodium value during hospitalization compared with patients who had not experienced another episode. The severity of hyponatremia, defined as minimum sodium value during hospitalization with a cut-off value of 110 mmol/l, and not obtaining sodium correction during hospitalization significantly correlated with overall survival rate. CONCLUSIONS: Hyponatremia due to SIADH could result in longer hospitalization and in a decreased overall survival when not adequately treated, and tolvaptan represents an effective treatment with a potential effect of both improving overall survival and decreasing duration of hospitalization.

Prolonged Drainage and Intrapericardial Bleomycin Administration for Cardiac Tamponade Secondary to Cancer-Related Pericardial Effusion.

Malignant pericardial effusion (MPE) is a serious complication of several cancers. The most commonly involved solid tumors are lung and breast cancer. MPE can give rise to the clinical picture of cardiac tamponade, a life threatening condition that needs immediate drainage. While simple pericardiocentesis allows resolution of the symptoms, MPE frequently relapses unless further procedures are performed. Prolonged drainage, talcage with antineoplastic agents, or surgical creation of a pleuro-pericardial window are the most commonly suggested ones. They all result in MPE resolution and high rates of long-term control. Patients suitable for further systemic treatments can have a good prognosis irrespective of the pericardial site of disease. We prospectively enrolled patients with cardiac tamponade treated with prolonged drainage associated with Bleomycin administration. Twenty-two consecutive patients with MPE and associated signs of hemodynamical compromise underwent prolonged drainage and subsequent Bleomycin administration. After injection of 100 mg lidocaine hydrochloride, 10 mg Bleomycin was injected into the pericardial space. The catheter was clumped for 48 h and then reopened. Removal was performed when the drainage volume was <25 mL daily. Twelve patients (54%) achieved complete response and 9 (41%) a partial response. Only 1 (5%) had a treatment failure and underwent a successful surgical procedure. Acute toxicity was of a low degree and occurred in 7 patients (32%). It consisted mainly in thoracic pain and supraventricular arrhythmia. The 1-year pericardial effusion progression-free survival rate was 74.0% (95% confidence interval [CI]: 51.0-97.3). At a median follow-up of 75 months, a pericardial progression was detected in 4 patients (18%). One- and two-year overall survival rates were 33.9% (95% CI: 13.6-54.2) and 14.5% (95% CI: 0.0-29.5), respectively, with lung cancer patients having a shorter survival than breast cancer patients. The worst prognosis, however, was shown in patients not suitable for systemic treatments, irrespective of the site of the primary tumor.Prolonged drainage and intrapericardial Bleomycin is a safe and effective treatment, which should be considered as first choice at least in patients suitable for active systemic treatment.

Hospital admission of cancer patients: avoidable practice or necessary care?

BACKGROUND: Cancer patients are frequently admitted to hospital due to acute conditions or refractory symptoms. This occurs through the emergency departments and requires medical oncologists to take an active role. The use of acute-care hospital increases in the last months of life. PATIENTS AND METHODS: We aimed to describe the admissions to a medical oncology inpatient service within a 16-month period with respect to patients and tumor characteristics, and the outcome of the hospital stay. RESULTS: 672 admissions of 454 patients were analysed. The majority of admissions were urgent (74.1%), and were due to uncontrolled symptoms (79.6%). Among the chief complaints, dyspnoea occurred in 15.7%, pain in 15.2%, and neurological symptoms in 14.5%. The majority of the hospitalizations resulted in discharge to home (60.6%); in 26.5% the patient died and in 11.0% was transferred to a hospice. Admissions due to symptoms correlated with a longer hospital stay and a higher incidence of in-hospital death. CONCLUSION: We suggest that hospital use is not necessarily a sign of inappropriately aggressive care: inpatient care is probably an unavoidable step in the cancer trajectory. Optimization of inpatient supportive procedures should be a specific task of modern medical oncology.

Is the combination of Cetuximab with chemo-radiotherapy regimens worthwhile in the treatment of locally advanced head and neck cancer? A review of current evidence.

The administration of Cetuximab in combination with radiotherapy and chemotherapy has shown clear survival improvements within the locally advanced and the relapsed/metastatic settings respectively. These results have provided the clinical rational for the inclusion of Cetuximab into chemo-radiation regimens. Trials assessing the combination of Cetuximab with induction chemotherapy, concomitant chemo-radiotherapy or both are reviewed. Taken together, their results suggest that the addition of Cetuximab is promising in trials of induction chemotherapy, showing almost uniformly response rates higher than historical controls. In combination with concomitant hyperfractionated radiotherapy and Cisplatin the results of the RTOG 0522 trial do not suggest any benefit. However a positive effect cannot be excluded with other schedules. Although feasibility has been universally suggested, adding Cetuximab implies some toxicity enhancement. Single local and systemic toxicities are more frequent and supposedly the overall treatment intensity is increased. Moreover the drug-specific toxicities are potentially severe and deserve timely recognition and management.