Efficacy of Large Use of Combined Hypofractionated Radiotherapy in a Cohort of Anti-PD-1 Monotherapy-Treated Melanoma Patients.

To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, 50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan−Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1−2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% [95% CI: 26.1−38.9]) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 [13.4−26.6] and 37.0 months [24.6−NA], respectively, in radiated patients, and 2.2 [1.5−2.6] and 4.3 months [2.6−7.1], respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6−25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.

Breast-conserving therapy can be offered to women with prior breast augmentation.

INTRODUCTION: Breast cancer in women with cosmetic breast implants is increasingly common. Over the past decade, there has been a push for mastectomy and reconstruction in these patients, based on a fear of poor aesthetic results from small breast volume, and radiation-induced capsular contracture. At the Paris Breast Centre, augmented women routinely undergo lumpectomy with whole-breast irradiation (BCT). MATERIALS AND METHODS: A consecutive cohort of 50 augmented women, who had attempted BCT for early breast cancer at our institution between 2003 and 2018, were retrospectively identified. Post-treatment complications, oncologic outcomes, capsular contracture rates, long-term cosmetic outcomes, and patient-reported outcomes were evaluated. RESULTS: The median follow-up was 51 months. Margins were involved in 7 women (14%); 4 of whom underwent successful re-excision, and 3 had a mastectomy, for an early mastectomy rate of 6%. There were no early complications, nor cases of early implant loss. Long-term aesthetic results were evaluated using our 5-point scale: An excellent (5), or good (4) result was obtained in 68%. Significant capsular contracture (Baker grade 3 or 4) developed in 34%, of which, 5 women underwent capsulotomy and fat grafting; 4 of 5 downstaging their Baker grade. The estimated 5-year local recurrence rate was 2.3%. Ninety-five percent of participants would recommend BCT to augmented women. CONCLUSION: BCT is feasible and safe in augmented women with good long-term aesthetic results, and should be considered to avoid unnecessary mastectomy.

Efficacy of late concurrent hypofractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy.

Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3-5 sessions, 20-26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95% CI: 8.0 not achieved (na)] and 35.3 [95% CI: 18.5 na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed.

Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients.

OBJECTIVE: To evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA). MATERIALS AND METHODS: Seventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates. RESULTS: The 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13-4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22-4.82]; p = 0.011, respectively). CONCLUSION: PTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.

Artificial Ascites for Pain Relief During Microwave Ablation of Subcapsular Liver Tumors.

PURPOSE: To compare post-procedure pain of subcapsular hepatic metastasis treated with microwave ablation (MWA) with and without artificial ascites. MATERIALS AND METHODS: During a 2-years period, 41 patients underwent MWA of 52 peripheral liver metastases including 20 patients (10 men and 10 women (mean ± SD age: 62 ± 9.3 years) who underwent MWA of 27 metastasis without artificial ascites (group 1), and 21 patients (12 men and 9 women (mean age: 63.5 ± 9.9 years) who underwent MWA of 25 metastasis with artificial ascites (group 2). Patient's pain assessment cores [10-point visual analog scale (VAS)] at 6, 24 h, and 4 days after the MWA procedure were compared among groups, as well as 24 h cumulative morphine dose was also compared among groups. Complications were reported. Statistical significance was evaluated by Fisher's exact test and Student's t test. RESULTS: Pain VAS were 8.6 ± 2.7, 3.9 ± 1.4, and 0.6 ± 1.2 at 6, 24 h, 4 days, respectively, for group-I and 0.8 ± 1.9, 0.3 ± 0.9, and 6.6 ± 3.5 for group II. Pain VAS were significantly different at 6, 24 h, and 4 days between the two groups (p < 0.0001). The average 24 h dose of morphine was 5.8 ± 2.2 mg in group-I and 0.2 ± 0.6 mg in group-II (p < 0.0001). Complications occurred in two patients from group-I (10%), including one bilio-pleural fistula and one minor cutaneous burn. One patient (9.5%) in group-II developed a lobar infarction. No bleeding and no procedure-related death were reported. CONCLUSION: Artificial ascites prevents immediate post-procedural pain, which re-appears intensively 4 days later.

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

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

[Conservative treatment undifferentiated neuroendocrine tumors of the anal canal: two cases]. / Traitement conservateur des tumeurs endocrines peu différenciées du canal anal.

Undifferentiated neuroendocrine tumors are rare, and are characteristically aggressive with a poor prognosis. Most patients have metastatic disease at diagnosis, and cannot undergo curative surgical treatment. A chemotherapy regimen combining etoposide plus cisplatin is currently considered to be the reference treatment. We report two cases of poorly differentiated neuroendocrine tumors localized in the anal canal and treated by chemotherapy and radiotherapy resulting in prolonged complete local remission and preventing extended surgical excision.

Chemotherapy as initial treatment of locally advanced unresectable pancreatic cancer: a valid option?

INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow-up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy.

Long-term results of breast cancer irradiation treatment with low-dose-rate external irradiation.

PURPOSE: The aim of this study was to assess beam therapy with low-dose-rate (LDR) external irradiation in a group of patients with breast cancer. METHODS AND MATERIALS: This trial compared, from 1986 to 1989, patients with advanced breast cancer treated either by conventional fractionation or low-dose-rate (LDR) external radiotherapy (dose-rate 15 mGy/min, 5 sessions of 9 Gy delivered on 5 consecutive days). RESULTS: A total of 21 patients were included in the fractionated therapy arm. At follow-up 15 years after treatment, 7 local recurrences had occurred, 3 patients had died of cancer, 18 patients were alive, 10 were without evidence of disease, and 6 had evidence of disease. A total of 22 patients had been included in the LDR arm of the study. Of these, 11 had received a dose of 45 Gy; thereafter, in view of severe local reactions, the dose was reduced to 35 Gy. There was no local recurrence in patients who had received 45 Gy, although there were 2 local recurrences among the 11 patients after 35 Gy. The sequelae were severe in patients who received 45 Gy but were comparable to those observed in patients treated by fractionated radiotherapy who received 35 Gy. The higher efficacy of tumor control in patients treated by LDR irradiation as well as the lower tolerance of normal tissue are probably related to the lack of repopulation. CONCLUSION: Although the patient numbers in this study are limited, based on our study results we conclude that the data for LDR irradiation are encouraging and that further investigation is warranted.

Urinary continence after salvage radiation therapy following radical prostatectomy, assessed by a self-administered questionnaire: a prospective study.

OBJECTIVE: To evaluate urinary continence after salvage radiotherapy following radical prostatectomy (RP) for clinically localized prostate cancer. PATIENTS AND METHODS: In all, 145 men had a retropubic RP in our department between 1992 and 2000. From this group, salvage radiotherapy with the dose of 65 Gy was given to 18 patients for a rising prostatic specific antigen (PSA) level. The mean (range) age at RP was 63 (50-72) years and the initial PSA level 14.95 (4.8-34) ng/mL. The radiotherapy was given at 46 (6-96) months after RP. A self-administered questionnaire about their urinary status was mailed to the patients before and 18 months after radiotherapy. The mean follow-up after radiotherapy was 34 (20-70) months. RESULTS: Before radiotherapy, 17 patients were continent (defining continence as no regular use of pads). After salvage radiotherapy, 16 men had had no change in their urinary status, even for the one patient using pads. One patient with stress urinary incontinence showed a slight worsening of his urinary status after radiotherapy. Another patient who was continent before radiotherapy developed urgency with no urinary leakage. Fourteen men stated that they were very satisfied or satisfied about their urinary status after radiotherapy and four were mildly satisfied. Nine would undergo radiotherapy again even with their present continence status and nine probably would. CONCLUSION: Using an anonymous self-administered questionnaire, salvage radiotherapy for a rising PSA level seems to be safe and does not worsen the continence achieved after RP in most patients.