Long-term outcomes of SBRT for PSMA PET detected oligometastatic prostate cancer.

BACKGROUND: Oligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to defer androgen deprivation and may deliver sustained biochemical failure (BF) free survival in selected patients. Little long-term data is currently available regarding the effectiveness of this approach. METHODS: A retrospective single institution study of PSMA-PET directed SBRT without initial ADT for oligo-metachronous PCa. Median dose/fractionation was 24 Gy in 2# to bones and 30 Gy in 3# to lymph nodes. The primary endpoint was time to BF (PSA + 0.2 ug/L above nadir). Secondary endpoints included time to ADT for relapse (i.e. palliative ADT), BF defined as PSA nadir + 2 ug/L, toxicity, patterns of failure and survival. Patients were excluded if they received ADT with their SBRT, had short disease-free interval, or > 3 metastases on PSMA-PET. RESULTS: 103 patients treated from November-2014 to December-2019 were analysed from our prospective database. Median follow-up was 5 years. 64 patients were treated for nodal only disease, 35 bone only and 4 mixed. 15% were free of any BF at 5 years with median time to BF of 1.1 years. 32% (33/103) of patients had further curative-intent radiation treatment following their first BF after SBRT, including subsequent SBRT. Eight patients underwent potentially curative treatment for their second or third relapse. Allowing for salvage treatment, 29/103 (28%) were biochemically disease free at last follow up. At 5 years, 39% of patients had never received any ADT and 55% had not started ADT for relapse with a median time to ADT for relapse of 5.5 years. There were 2 grade 3 toxicities (rib fracture and lymphoedema), and no local failures. CONCLUSION: PSMA-PET guided SBRT for oligo-metachronous PCa recurrence in appropriately triaged patients results in excellent local control, low toxicity and over 50% ADT free at 5 years.

Ductal Carcinoma of the Prostate: An Uncommon Entity With Atypical Behaviour.

AIMS: Ductal adenocarcinoma is a rare variant of prostate cancer, and as such clinical outcomes and best management are not well defined. This series demonstrates the atypical presentation and unusual clinical behaviour of ductal adenocarcinoma and proposes management guidelines to assist clinicians. MATERIALS AND METHODS: A retrospective review of pure (nine patients) and mixed (18 patients) ductal adenocarcinoma of the prostate referred to the Departments of Radiation Oncology of the Sydney Cancer Centre, Royal Prince Alfred Hospital and Northern Sydney Cancer Centre, Royal North Shore Hospital, between 2000 and 2015. RESULTS: Twenty-seven patients were treated with definitive radiotherapy, nine patients (33%) with pure ductal and 18 (67%) with mixed ductal-acinar adenocarcinoma. The median follow-up was 38 months. Four patients (15%) failed locally, all of whom received less than 80 Gy, or no brachytherapy boost. Five patients (19%) failed distantly, four with biopsy-proven lung metastases. All distant failures occurred with a prostate-specific antigen (PSA) < 3 ng/ml. CONCLUSION: This series shows the atypical clinical presentation of this entity, as well as its propensity to metastasise to unusual sites. Relapse may occur at low absolute PSA values and is often asymptomatic. Ductal cancer should not simply be regarded as a high Gleason grade cancer. We propose management guidelines, including regular computed tomography examinations (rather than relying solely on PSA levels) as part of the follow-up for patients with any component of ductal adenocarcinoma.

Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high volume referral centre.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to surgery provides promise. In the absence of prospective data, well annotated clinical data from high-volume units may provide pilot data for randomised trials. METHODS: Medical records from a tertiary hospital in Sydney, Australia, were analysed to identify all patients with resectable or borderline resectable PDAC. Data regarding treatment, toxicity and survival were collected. RESULTS: Between January 1 2010 and April 1 2016, 220 sequential patients were treated: 87 with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5 UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline patients received NA RT, 22 sequential to NAC. The median overall survival (OS) in the NA group was 25.9 months (mo); 95% CI (21.1-43.0 mo) compared to 26.9 mo (19.7, 32.7) in the UO; HR 0.89; log-ranked p-value = 0.58. Sixty-nine NA patients (79%) were resected, mOS was 29.2 mo (22.27, not reached (NR)). Twenty-two NA (31%) versus 22 UO (17%) were node negative at operation (N0). In those managed with NAC/RT the mOS was 29.0 mo (17.3, NR). There were no post-operative deaths with NA within 90-days and three in the UO arm. DISCUSSION: This is a hypothesis generating retrospective review of a selected real-world population in a high-throughput unit. Treatment with NA was well tolerated. The long observed survival in this group may be explained by lymph node sterilisation by NA, and the achievement of R0 resection in a greater proportion of patients.

Late Genitourinary Toxicity Outcomes in 300 Prostate Cancer Patients Treated With Dose-escalated Image-guided Intensity-modulated Radiotherapy.

AIMS: To quantify and qualify late genitourinary toxicity in a cohort of patients with localised prostate cancer treated with image-guided intensity-modulated radiotherapy (IMRT) to doses ≥78 Gy. MATERIALS AND METHODS: The cohort consisted of 300 patients treated with definitive dose-escalated IMRT between 2007 and 2013. Ninety-seven patients received 78-80 Gy in 38 fractions, and 203 received 82-84 Gy in 40 fractions. International Prostate Symptoms Score (IPSS) and supplemental quality of life data were recorded at baseline, weekly during treatment and at follow-up. Genitourinary toxicities were recorded using modified Radiation Therapy Oncology Group criteria during weekly treatment review and at each follow-up. Kaplan-Meier curves were used to assess the cumulative incidence of grade ≥ 2 genitourinary toxicity at 3 years. Baseline patient characteristics and symptoms were then used in univariate and multivariate analyses to identify predictors of late urinary toxicity. RESULTS: The median follow-up was 58 months (range 9-109 months). The actuarial cumulative 3 year rates of grade ≥ 2 and grade 3 genitourinary toxicity were 14.9% and 2.8%, respectively. There was no grade 4 toxicity. History of transurethral resection of the prostate (TURP), alpha blocker use before radiation, any hormone use, baseline IPSS ≥ 14 and pre-existing incontinence or nocturia were significantly associated with late ≥ 2 genitourinary toxicity on univariate analysis. On multivariate analysis, only previous TURP retained significance, with a hazard ratio of 2.54 (P=0.002). CONCLUSION: Our study showed acceptable levels of late grade 2 genitourinary toxicity and low rates of late grade 3 genitourinary toxicity in a cohort of patients with prostate cancer treated with image-guided IMRT to doses between 78 and 84 Gy. Variables associated with increased late ≥ 2 genitourinary toxicity include previous TURP, alpha blocker use, hormone use and pre-existing urinary dysfunction.

SpaceOAR Hydrogel in Dose-escalated Prostate Cancer Radiotherapy: Rectal Dosimetry and Late Toxicity.

AIM: To investigate the feasibility, dosimetric benefits and late toxicity of a temporary hydrogel spacer between the rectum and the prostate for prostate intensity-modulated radiotherapy. MATERIALS AND METHODS: Thirty patients with prostate cancer were enrolled on a phase I/II study. All patients underwent magnetic resonance imaging before and after placement of 10 cm(3) of hydrogel. The first 10 patients had an additional magnetic resonance imaging after the completion of radiation treatment. SpaceOAR hydrogel was injected under general anaesthetic using a transperineal approach with transrectal ultrasound guidance. Primary end points were perioperative toxicity and comparison of rectal dosimetry. Secondary end points included cute and late radiation toxicity. All patients were planned on both pre- and post-hydrogel scans to a D95 of 80 Gy in 40 fractions. A contemporary control group of 110 prostate cancer patients treated with the same prescription was identified for comparison. RESULTS: There were no perioperative complications. Rectal doses were significantly lower for the post-hydrogel plans, especially above 65 Gy (V82 = 0.2% versus 1.3%; V80 = 0.8% versus 5.3%; V75 = 2.2% versus 9.5%; V70 = 3.7% versus 12.3%; V65 = 5.4% versus 14.7%; V40 = 22.9% versus 32% and V30 = 42.7% versus 49.4%). There was no significant difference in acute grade 1 and 2 gastrointestinal toxicity, which was 43% versus 51% and 0% versus 4.5% in the hydrogel and control groups, respectively. Late grade 1 was significantly less frequent in the hydrogel group (16.6% versus 41.8%, P = 0.04). CONCLUSION: SpaceOAR hydrogel was inserted with minimal side-effects. Dosimetric benefits were greatest at higher rectal doses (V65 to V82). Late grade 1 gastrointestinal toxicity was significantly lower than that seen in patients treated without hydrogel.

Compliance of males with stage 1 testicular germ cell tumours on an active surveillance protocol.

The aim of this retrospective study was to determine the rate of compliance among 57 males with stage 1 testicular germ cell tumours on an active surveillance protocol at a single Australian centre. At median follow up of 24 months, 81% had adequate compliance with the follow-up regimen, 12% were lost to follow up, and 16% relapsed; none between protocol visits. Active surveillance is an acceptable alternative to adjuvant therapy for stage 1 testicular germ cell tumours, with reduced toxicity for most and equivalent survival, but requires efforts to maintain adequate compliance with follow up to avoid late detection of recurrence.

Implementing Intensity-modulated Radiotherapy with Simultaneous Integrated Boost for Anal Cancer: 3 Year Outcomes at Two Sydney Institutions.

AIMS: Modern chemoradiotherapy used for the treatment of anal cancer has significant acute toxicity. Intensity-modulated radiotherapy (IMRT) may reduce these side-effects. We report our experience implementing IMRT with simultaneous boost at the Sydney Cancer Centre and Royal North Shore Hospital. MATERIALS AND METHODS: We retrospectively collected acute toxicity data on all consecutive patients treated definitively with IMRT between January 2008 and December 2011. Patients received concurrent 5-fluorouracil and mitomycin-C. The radiotherapy dose varied by stage in accordance with the Radiation Therapy Oncology Group (RTOG) 0529 protocol. The first 30 plans were evaluated for adherence to RTOG 0529 dose specifications. Locoregional control and survival outcomes were analysed in July 2014. RESULTS: We included 42 patients (stage I 12%; II 41%; III 45%) with a median follow-up time of 43 months. At 3 years the locoregional control was 94% (95% confidence interval: 78-99), overall survival was 92% (95% confidence interval: 78-97), disease-free survival was 89% (95% confidence interval: 73-96), metastasis-free survival was 89% (95% confidence interval: 73-96) and colostomy-free survival was 89% (95% confidence interval: 72-96). There was no acute grade 4 toxicity. Acute grade 3 toxicity rates were: dermatological (33%), gastrointestinal (14%) and haematological (19%). Twenty-six per cent of patients were hospitalised for treatment-related toxicity. Only 12% required a treatment break greater than 3 days. All patients achieved RTOG 0529 planning target volume dose specifications. Most critical organ dose constraints were either met or met with minor deviation. The exception was 76% major deviation in small bowel constraints. Despite this no increase in gastrointestinal toxicity was observed. CONCLUSIONS: IMRT with simultaneous integrated boost is safe and well tolerated in an unselected population. Most dose specifications are achievable. Excellent locoregional control and survival outcomes are achievable outside of a clinical trial setting.

Attentional bias and metacognitions in cancer survivors with high fear of cancer recurrence.

BACKGROUND: Fear of cancer recurrence (FCR) is a common and severe problem amongst cancer survivors, but mechanisms to explain its development and maintenance are still lacking. The self-regulatory executive function (S-REF) model suggests that metacognitions and attentional bias to cancer-related words may explain high FCR. Thus, this study aimed to explore relationships between FCR, metacognitions and attentional bias in a mixed group of cancer survivors. METHOD: Sixty-three early-stage breast or prostate cancer survivors, diagnosed within 6 months to 5 years prior to participation and who had completed all hospital-based treatment with no evidence of cancer recurrence were recruited through two metropolitan oncology clinics. Participants completed a questionnaire battery and the dot-probe task. RESULTS: Survivors with clinical FCR had significantly greater positive beliefs about worry (10.1 vs 7.4, p = 0.002) and beliefs about the uncontrollability and danger of worry (12.0 vs 7.7, p = 0.000) than those with non-clinical FCR, whereas the total metacognition score significantly predicted FCR in multiple regression analysis (ß = 0.371, p = 0.001). No significant differences were detected between participants scoring above and below clinical FCR levels in attention bias indices. CONCLUSIONS: This study found partial support for the S-REF model of FCR, with metacognitions but not attentional bias found to be related to FCR. Further research is needed to explore attentional biases in more detail.

The important role of radiation treatment in the management of Merkel cell carcinoma.

Merkel cell carcinoma is an aggressive, radiosensitive cutaneous neuroendocrine tumour. In this review, the roles of radiation therapy and chemoradiation in the management of Merkel cell carcinoma are described and discussed, and guidelines for patient management are presented. Radiation treatment may be indicated for definitive (> 55 Gy) or adjuvant (> 50 Gy) treatment of the primary tumour site and for prophylactic (> 50 Gy), adjuvant (> 50 Gy) or definitive (> 55 Gy) treatment of the regional lymph node field. If a patient presents with positive margins after initial biopsy or resection, definitive radiation therapy or chemoradiation may be an alternative to further surgery and, importantly, results in less delay than re-resection followed by adjuvant radiation treatment. Given the rarity of this tumour, patients should be enrolled on prospective databases and clinical trials, and managed in a multidisciplinary clinical setting wherever possible.

Biopsy-proven brain metastases from prostate cancer: a series of four cases with review of the literature.

AIMS: Prostate cancer is very common and is the second most common cause of cancer death in males in Australia; however, brain metastases are exceedingly rare. MATERIALS AND METHODS: We review four cases of biopsy-proven brain metastases from prostate cancer and review the relevant literature. RESULTS: Three of four patients had acinar adenocarcinoma of prostate with one patient having ductal adenocarcinoma variant on histopathology. Three patients had the brain as the only site of metastatic disease. All patients underwent surgery, and three of four patients underwent adjuvant palliative radiotherapy to the brain. CONCLUSION: Brain metastases from prostate cancer are rare, but brain metastases without other sites of metastatic disease are exceedingly rare and may be more common with ductal adenocarcinoma variant.

Definitive radiotherapy or chemoradiotherapy in the treatment of Merkel cell carcinoma.

AIMS: Merkel cell carcinoma (MCC) is a radiosensitive tumour. Radiotherapy has an important role in its treatment, including definitive management. This study aimed to determine the in-field control achieved with definitive radiotherapy or chemoradiotherapy (CRT) and to examine patterns of relapse. MATERIALS AND METHODS: Patients treated with definitive radiotherapy or CRT for biopsy-confirmed MCC were identified from records of the Royal Prince Alfred Hospital and Melanoma Institute Australia. Definitive treatment was defined as treatment delivered to macroscopic or residual microscopic disease at the primary site or in regional nodes. Patients with distant metastatic disease at presentation and those treated electively or adjuvantly (i.e. after microscopically clear excision) were excluded. RESULTS: Of 26 patients treated with definitive radiotherapy (n = 18) or CRT (n = 8), 20 were disease free at last follow-up (median follow-up 23.5 months). Five of the six patients who recurred did so at distant sites, with two experiencing simultaneous in-field failure at treated nodal sites where there had been macroscopic disease at presentation. Eighty-nine per cent of all patients and 85% of those with macroscopic disease were free of in-field recurrence at 2 years. CONCLUSION: Definitive radiotherapy or CRT produces excellent in-field disease control in the treatment of primary and regionally metastatic MCC.

The GOFURTGO Study: AGITG phase II study of fixed dose rate gemcitabine-oxaliplatin integrated with concomitant 5FU and 3-D conformal radiotherapy for the treatment of localised pancreatic cancer.

BACKGROUND: Locally advanced inoperable pancreatic cancer (LAPC) has a poor prognosis. By increasing intensity of systemic therapy combined with an established safe chemoradiation technique, our intention was to enhance the outcomes of LAPC. In preparation for phase III evaluation, the feasibility and efficacy of our candidate regimen gemcitabine-oxaliplatin chemotherapy with sandwich 5-fluorouracil (5FU) and three-dimensional conformal radiotherapy (3DCRT) needs to be established. METHODS: A total of 48 patients with inoperable LAPC without metastases were given gemcitabine (1000 mg m(-2) d1 + d15 q28) and oxaliplatin (100 mg m(-2) d2 + d16 q28) in induction (one cycle) and consolidation (three cycles), and 5FU 200 mg m(-2) per day over 6 weeks during 3DCRT 54 Gy. RESULTS: Median duration of sustained local control (LC) was 15.8 months, progression-free survival (PFS) was 11.0 months, and overall survival was 15.7 months. Survival rates for 1, 2, and 3 years were 70.2%, 21.3%, and 12.8%, respectively. Global quality of life did not significantly decline from baseline during treatment, which was associated with modest treatment-related toxicity. CONCLUSION: Fixed-dose gemcitabine and oxaliplatin, combined with an effective and safe regimen of 5FU and 3DCRT radiotherapy, was feasible and reasonably tolerated. The observed improved duration of LC and PFS with more intensive therapy over previous trials may be due to patient selection, but suggest that further evaluation in phase III trials is warranted.

Review of 120 anal cancer patients.

OBJECTIVE: Chemoradiotherapy is the mainstay of treatment for the majority of patients with anal cancer, with abdominoperineal resection reserved for salvage. The purpose of this study was to evaluate our results after radiotherapy with or without chemotherapy, and/or surgery in terms of overall survival and colostomy free survival in patients with anal cancer. METHOD: A review of patients diagnosed with anal cancer between 1991 and 2004 was performed. The principle end-points of the study were overall and colostomy-free survival. RESULTS: One hundred and twenty patients were identified. The T stage distribution was T1 32, T2 44, T3 19, T4 17 and TX 8. Eighteen patients had clinically involved regional nodes. Eighty patients received radiotherapy as a component of their treatment. Twenty-four of the 80 patients had a colostomy. The most common late toxicity was faecal incontinence. The overall survival and colostomy-free survival rates for all 120 patients were 58% and 79% at 5 years, respectively. For the 80 patients who received radiotherapy, the corresponding figures were 66% and 82% at 5 years, respectively. CONCLUSION: Chemoradiation is effective organ preserving treatment for anal cancer. Grade 1 and 2 faecal incontinence is a relatively common late toxicity experienced by patients.

An audit of analgesia requirements for high-dose-rate prostate brachytherapy.

We audited the analgesic, anti-emetic and anti-spasmodic drug usage of patients undergoing high-dose-rate brachytherapy for prostate cancer at the Royal Prince Alfred Hospital. With institutional ethics committee approval, we retrospectively reviewed the records of the first 45 patients undergoing high-dose-rate prostate brachytherapy from January 2003 to July 2005. We collected data regarding the dose of intra- and postoperative analgesics and the anti-emetic and anti-spasmodic drugs administered for the duration of the patients' hospital stay. We converted oral oxycodone doses to parenteral morphine equivalents for the purposes of this study, dividing the oxycodone dose by three. The median age of the patients was 69 (range 55 to 80) years. All had general anaesthesia for the catheter insertion procedure. Twenty-five patients (56%) received intraoperative morphine from 5 to 12 mg (mean 9 mg). Forty-three patients (96%) received regular postoperative paracetamol (1 g qid). Thirty-six patients (80%) required additional postoperative opioid administration with an overall mean (all 45 patients included) of 14.5 mg of parenteral morphine equivalents over the entire postoperative course. Thirty-nine patients received intraoperative hyoscine butylbromide to reduce bladder spasm. Fourteen patients were administered antiemetics. These findings indicate that analgesic requirements during the period in which the prostate brachytherapy catheters remained in place were minimal in most cases. Simple analgesic regimens (regular oral paracetamol, antispasmodics as required for bladder spasm and oral/subcutaneous opioids as required) appear to have been adequate for our patients.

Consumer impact of an interactive decision aid for rectal cancer patients offered adjuvant therapy.

OBJECTIVE: There is increasing interest in the use of decision aids (DAs) to facilitate patient involvement in clinical decisions. This study explored the views of patients with colorectal cancer and participants in a community bowel screening service regarding an interactive DA concerning adjuvant treatment for rectal cancer, and the impact of the aid on knowledge, anxiety, attitudes and preferences for treatment options. METHOD: Fourteen patients with colorectal cancer participated in four focus groups. Eighty-nine participants in a community bowel screening service completed a questionnaire before and 1 week after viewing the DA. Thirty were randomly selected to participate in a telephone interview to obtain qualitative feedback about the DA. RESULTS: Focus group participants reported using information to evaluate their doctor's care and expertise, or to prepare themselves for future symptoms and side-effects. Most supported the use of a DA and preferred pie charts to convey risk information. Within the community sample, anxiety remained stable and knowledge increased after exposure to the DA. Almost all participants found the DA useful and easy to understand, and felt it would make the process of decision making easier. CONCLUSION: A DA regarding adjuvant therapy for rectal cancer appears to be valued and to produce positive outcomes. A randomized controlled trial of this intervention is now required.

Management preferences following radical inguinal orchidectomy for Stage I testicular seminoma in Australasia.

A survey to evaluate the preferred patterns of management of Stage I seminoma was conducted during March 2001. The questionnaire was distributed by the Royal Australian and New Zealand College of Radiologists to all qualified radiation oncologists, 74 out of 170 responded. All performed a staging CT scan of the abdomen and pelvis. Thoracic imaging consisted of either chest X-ray (29%) or chest CT (38%) while 33% performed both. Fifty-four percent of radiation oncologists discussed surveillance with their patients but estimated that 5% or less would choose this option. The most commonly prescribed dose was 25 Gy in 15 or 20 fractions (79%). Sixty-five percent of respondents treated the para-aortic (PA) nodes alone. Forty-two of 48 clinicians treating the PA field reported a change in practice after publication of the Medical Research Council study in 1999. Of these, 40 and 23% perform CT scans of the pelvis annually and every 6 months. Thirty-one percent did no follow-up CT scan. Compared to a similar survey from North America, we are more likely to use PA fields and less likely to discuss surveillance. As in the USA, and in contrast to Canada, few patients choose surveillance. There is no consensus regarding the frequency of follow-up scans in either North America or Australasia.

Prospective patient-based assessment of effectiveness of palliative radiotherapy for bone metastases.

PURPOSE: The primary objective of this report is to prospectively evaluate pain control provided by palliative radiotherapy for all irradiated patients with bone metastases by using their own assessments. MATERIALS AND METHODS: A prospective database was set up for all patients referred for palliative radiotherapy for bone metastases. Patients were asked to rate their pain intensity using an 11 categorical point scale (0=lack of pain, 10=worst pain imaginable). Analgesic consumption during the preceding 24 h was recorded and converted into equivalent total daily dose of oral morphine. For those who received radiotherapy, follow-up was conducted via telephone interviews at week 1, 2, 4, 8 and 12 post treatment using the same pain scale and analgesic diary. Radiotherapy outcome was initially assessed by pain score alone. Complete response (CR) was defined as a pain score of 0. Partial response (PR) was defined as a reduction of score > or =2 or a> or =50% reduction of the pre-treatment pain score. We further analyzed outcomes using integrated pain and analgesic scores. Response was defined as either a reduction of pain score > or =2 with at least no increase in analgesics or at least stable pain score with a > or =50% reduction in analgesic intake. RESULTS: One hundred and five patients were treated with palliative radiotherapy. When response evaluation was by pain score alone, the PR rates at 2, 4, 8 and 12 weeks were 44, 42, 30 and 38%, respectively; while the CR rates were 24, 32, 31 and 29%, respectively. The overall response rate at 12 weeks was 67%. When assessed by the integrated pain and analgesic scores, the response rates were 50, 46, 43 and 43%, respectively. CONCLUSION: The response rate in our patient population is comparable with those reported in clinical trials. This is important when counselling our patients on the expected effectiveness of radiotherapy outside of clinical trials. Our observations confirm the generalizability of the trials conducted to date. While randomized trials still remain the gold standard of research, observational studies can serve as useful adjuncts to randomized trials to confirm the efficacy and guide the design of new controlled trials.

Combined large cell neuroendocrine carcinoma and spindle cell carcinoma of the lung.

We report a unique case of a combined pulmonary large-cell neuroendocrine carcinoma and spindle-cell carcinoma. The patient was a 54-year-old female smoker who presented with a 4-month history of increased left-sided chest pain and exertional dyspnea. The left upper lobectomy specimen revealed an 8.0-cm mass with central necrosis. Microscopically, the epithelial areas were composed of well-defined nests of large cells with peripheral palisading expressing low-molecular-weight keratin, synaptophysin, chromogranin, and neuron-specific enolase. The spindle-cell component consisted of pleomorphic cells arranged in fibrosarcoma and malignant fibrous histiocytoma-like patterns. These spindle cells were positive for low-molecular-weight keratin and vimentin with focal expression of CD68 and muscle-specific actin. Electron microscopy in the spindle-cell areas showed cell junctions and numerous tonofilaments, indicative of epithelial differentiation. The tumor behaved aggressively and the patient died with extensive metastases 4 months after surgery. The combination of neuroendocrine malignancies and spindle-cell carcinomas appears to be uncommon in the lung. Previous reports have described this association in single case reports of anaplastic small-cell carcinoma and atypical carcinoid, but not in large-cell neuroendocrine carcinoma.

Prospective assessment of symptom palliation for patients attending a rapid response radiotherapy program. feasibility of telephone follow-up.

Clinical trials generally include motivated patients with relatively good performance status. This can result in an overestimation of the effectiveness of an intervention. Clinic follow-up protocols for outcome assessment after palliative treatments suffer from high attrition rates. In this study, the feasibility of telephone follow-up for the assessment of symptom palliation in patients receiving outpatient palliative radiotherapy as a tool to evaluate outcome was examined. Patients referred for palliative radiotherapy were asked to rate their symptom distress using the modified Edmonton Symptom Assessment System (ESAS) at initial consultation. Patient demographics and analgesic consumption were collected. For those who received radiotherapy, follow-up was conducted through telephone interviews at week 1, 2, 4, 8, and 12 post-treatment using the same modified ESAS and analgesic diary. One hundred ninety patients received radiotherapy to 256 sites from January to August 1999. Seventy-eight patients (41%) died during the 12-week follow-up period. The percentage of surviving patients responding to the telephone interview ranged from 63% to 68% during the 12-week study. Telephone follow-up is a feasible tool for the prospective outcome assessment of symptom palliation in this population. It compares well to clinic visits or mailed questionnaires. However, to improve the follow-up rates, other modalities may also need to be implemented.