Collins Law and Estimating a Tumors Age before diagnosis

In Oncology last week:

An interesting article from Larry Marks - which gets at a question often heard in the clinic: "How long have I had this?" Marks uses a variation on Collins Law (well described in the paper) to estimate how long a tumor may have existed from the development of the first clonogen to the time of detection based on local recurrence rates after a curative resection, and finds that some tumors may have existed for many years prior to detection (3-6 years for the sites studied).

Now obviously there are huge assumptions: first that growth rates are similar before and after a curative surgery, and it excludes tumors which may have been treated more aggressively, and recurred distantly. Therefore, one can really only apply this to low grade cancers that are likely to fail locally only. Nonetheless, it's an interesting thought experiment.

Link (requires free membership to login)

How Long Have I Had My Cancer, Doctor? - Cancer Network

How Long Have I Got? Estimating Typical, Best-Case, and Worst-Case Scenarios for Patients Starting First-Line Chemotherapy for Metastatic Breast Cancer: A Systematic Review of Recent Randomized Trials [REVIEW ARTICLE]

In the JCO:

A relatively simple way to approach estimating a patient's long term prognosis with metastatic breast cancer is put forward in the JCO this week. I liked this as it is simple, in a way that hopefully will be useful to patients when considering their prognosis, going beyond the simple median survivals that immediately come to mind. Of course, one has to take into account that these are based on published clinical trials, which tend to attract and accrue the most motivated and healthy of patients.

Link and Abstract.

How Long Have I Got? Estimating Typical, Best-Case, and Worst-Case Scenarios for Patients Starting First-Line Chemotherapy for Metastatic Breast Cancer: A Systematic Review of Recent Randomized Trials [REVIEW ARTICLE]: "Purpose

To estimate scenarios for survival for women with metastatic breast cancer (MBC) who are starting chemotherapy.

Patients and Methods

We sought randomized, first-line chemotherapy trials for MBC published from 1999 to 2009. We recorded median progression-free survival (PFS) and median overall survival (OS) and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We also estimated these scenarios for each OS curve by multiplying its median by four simple multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). Estimates were deemed accurate if they were within 0.75 to 1.33 times the actual value.

Results

From 36 trials (13,083 women), the mean for median PFS was 7.6 months (interquartile range [IQR], 6.0 to 9.0 months), the mean for median OS was 21.7 months (IQR,18.2 to 24.0 months), and the mean for the ratio of median OS to median PFS was 3.0 (IQR, 2.4 to 3.5). The mean for each OS scenario was worst-case, 6.3 months (IQR, 4.8 to 7.5 months); lower-typical, 11.9 months (IQR, 9.9 to 13.2 months); upper-typical, 36.2 months (IQR, 31.1 to 41.3 months); and best-case, 55.8 months (IQR, 47.5 to 60.2 months). Simple multiples of the median gave accurate estimates of the worst-case scenario in 73% of OS curves, lower-typical in 97%, upper-typical in 95%, and best-case in 96%. OS was longer in trials with higher proportions of estrogen receptor–positive tumors (P = .001) and in trials of trastuzumab-treated human epidermal growth factor receptor 2–positive tumors (P = .001).

Conclusion

Simple multiples of an OS curve's median can accurately estimate typical (half to double the median), best-case (triple the median), and worst-case (one quarter of the median) scenarios for survival.

"

MDS in Atomic Bomb survivors

In the JCO:

Fortunately there are very few populations in which the late effects of single instance low dose whole body radiation can be studied. Fortunately also, the Japanese and US government have been very helpful in performing large scale studies of the long term effects of the two bombs dropped. While a fair amount of the secondary cancer risk has been published, from the data presented in JCO this week, MDS is clearly another risk that should be monitored for.

Links and Abstract:

Risk of Myelodysplastic Syndromes in People Exposed to Ionizing Radiation: A Retrospective Cohort Study of Nagasaki Atomic Bomb Survivors [Epidemiology]: "Purpose

The risk of myelodysplastic syndromes (MDS) has not been fully investigated among people exposed to ionizing radiation. We investigate MDS risk and radiation dose-response in Japanese atomic bomb survivors.

Patients and Methods

We conducted a retrospective cohort study by using two databases of Nagasaki atomic bomb survivors: 64,026 people with known exposure distance in the database of Nagasaki University Atomic-Bomb Disease Institute (ABDI) and 22,245 people with estimated radiation dose in the Radiation Effects Research Foundation Life Span Study (LSS). Patients with MDS diagnosed from 1985 to 2004 were identified by record linkage between the cohorts and the Nagasaki Prefecture Cancer Registry. Cox and Poisson regression models were used to estimate relationships between exposure distance or dose and MDS risk.

Results

There were 151 patients with MDS in the ABDI cohort and 47 patients with MDS in the LSS cohort. MDS rate increased inversely with exposure distance, with an excess relative risk (ERR) decay per km of 1.2 (95% CI, 0.4 to 3.0; P < .001) for ABDI. MDS risk also showed a significant linear response to exposure dose level (P < .001) with an ERR per Gy of 4.3 (95% CI, 1.6 to 9.5; P < .001). After adjustment for sex, attained age, and birth year, the MDS risk was significantly greater in those exposed when young.

Conclusion

A significant linear radiation dose-response for MDS exists in atomic bomb survivors 40 to 60 years after radiation exposure. Clinicians should perform careful long-term follow-up of irradiated people to detect MDS as early as possible.

"

Results of the SPIRIT trial (Surgery vs Brachy) for Prostate

In the JCO:

Few disease sites would benefit from a randomized trial more than prostate cancer would, though we can't seem to accrue anything except for varying lengths of hormonal treatment and different postoperative strategies. The SPIRIT trial valiantly tried to correct this issue, however unfortunately failed to accrue. Fortunately, at lease some data from this attempt is published in JCO this week, and the QOL in urinary and sexual domains favor brachytherapy. Link and abstract below.

Comparison of Health-Related Quality of Life 5 Years After SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial [Urologic Oncology]: "Purpose

The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy (RP) and brachytherapy (BT) closed after 2 years due to poor accrual. We report health-related quality of life (HRQOL) at a mean of 5.3 years for 168 trial-eligible men who either chose or were randomly assigned to RP or BT following a multidisciplinary educational session.

Patients and Methods

After initial lack of accrual, a multidisciplinary educational session was introduced for eligible patients. In all, 263 men attended 47 sessions. Of those, 34 consented to random assignment, 62 chose RP, and 94 chose BT. Five years later, these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Expanded Prostate Cancer Index Composite, the Short Form 12 Physical Component Score, and Short Form 12 Mental Component Score. Response rate was 88.4%. The Wilcoxon rank sum test was used to compare summary scores between the two interventions.

Results

Of 168 survey responders, 60.7% had BT (9.5% randomly assigned) and 39.3% had RP (9.5% randomly assigned). Median age was 61.4 years for BT and 59.4 for RP (P = .05). Median follow-up was 5.2 years (range, 3.2 to 6.5 years). For BT versus RP, there was no difference in bowel or hormonal domains, but men treated with BT scored better in urinary (91.8 v 88.1; P = .02) and sexual (52.5 v 39.2; P = .001) domains, and in patient satisfaction (93.6 v 76.9; P < .001).

Conclusion

Although treatment allocation was random in only 19%, all patients received identical information in a multidisciplinary setting before selecting RP, BT, or random assignment. HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction.

"

Lancet Oncology: Urorad and IMRT

A very blunt interview with Anthony Zeitman is published in Lancet Oncology, blasting the Urorad business model.

[News] US urology clinics overprescribe prostate radiotherapy: "The US Government Accountability Office is investigating allegations that urologists are reaping hundreds of millions of dollars by overprescribing intensity-modulated radiotherapy (IMRT) for prostate cancer. Since 2002, Medicare, the federal health insurance programme for elderly patients, has paid generously for IMRT—up to US$40 000 per patient."

Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity

In Cancer this week:

An analysis from Dr Alektiar at MSKCC retrospectively examines their experience with IMRT treating STS (soft tissue sarcoma), compared to a historical cohort of brachytherapy patients. Of course there are significant limitations in any retrospective analysis, but the local control was quite good with IMRT, with no significant difference in toxicity. Obviously one would prefer randomized data before accepting a new modality as standard of care, however, given the overall rarity of STS, and the broad acceptance of EBRT, it seems likely that this will be the treatment of choice moving forward.

Link and Abstract:

Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity: "

Abstract

BACKGROUND:

Based on results of a prospective randomized trial, brachytherapy (BRT) had been the preferred form of adjuvant radiotherapy for patients with high-grade extremity soft tissue sarcoma (STS) at our institution. In recent years, intensity-modulated radiotherapy IMRT had been increasingly used. This study compared local control by IMRT versus by BRT in primary-extremity STS.

METHODS:

Between January 1995 and December 2006, 134 adult patients with high-grade primary nonmetastatic STS of the extremity were treated at this institution with limb-sparing surgery and adjuvant radiotherapy (RT). Low-dose-rate BRT was given to 71 patients between January 1995 and November 2003 to a median dose of 45 Gray (Gy). IMRT was given between February 2002 and December 2006: preoperatively to 10 (50 Gy) and postoperatively to 53 (median, 63 Gy). Median follow-up was 46 months.

RESULTS:

Treatment groups were comparable in terms of gender, age, site, depth, histology (malignant fibrous histiocytoma vs other), and use of adjuvant chemotherapy. More IMRT patients had positive/close margins (<1 mm), large tumors (>10 cm), and bone or nerve stripping/resection (P = 0.006, 0.005, 0.02, and 0.002, respectively). Median follow-up was 46 months for IMRT and 47 months for BRT. Five-year local control was 92% (95% confidence interval [CI], 85-100) for IMRT versus 81% (95% CI, 71-90) for BRT, P = 0.04. On multivariate analysis, IMRT was the only predictor of improved local control, P = 0.04.

CONCLUSIONS:

Local control with IMRT was significantly better than BRT despite higher rates of adverse features for IMRT in this nonrandomized comparison. IMRT should be further examined as the treatment of choice for primary high-grade extremity sarcoma. Cancer 2011. © 2011 American Cancer Society.

"

DVH parameters for Cervical HDR brachytherapy

In the Red Journal this week:

A very interesting article from the Vienna group, exploring thresholds for late toxicity with cervical brachytherapy. They review 141 patients, and arrive at a threshold for significant (G2-4) late effects for the rectal D2cc of 75Gy. Their data for bladder is a little less well established, but they arrive at a threshold of 100Gy for D2cc. They could determine no thresholds for sigmoid toxicity as it was a very rare occurrence in their cohort.

One thing to note when interpreting this data is that the Vienna group gives 7Gy x 4 over the course of 1 weeks application, which is different that most US practice with brachy (5-6Gy in 5 fractions, with a frequency of ~2/week). While the doses reported are in EQD2 terms, one must realize that these conversions are based on theory and assumptions about alpha beta ratios which may not entirely apply to each brachy schedule. Nonetheless, this remains the best data around for modern 3D dosimetry in cervical brachytherapy.

Link and abstract

Dose–Volume Histogram Parameters and Late Side Effects in Magnetic Resonance Image–Guided Adaptive Cervical Cancer Brachytherapy: "Purpose: To evaluate the predictive value of dose–volume histogram (DVH) parameters for late side effects of the rectum, sigmoid colon, and bladder in image-guided brachytherapy for cervix cancer patients.Methods and Materials: A total of 141 patients received external-beam radiotherapy and image-guided brachytherapy with or without chemotherapy. The DVH parameters for the most exposed 2, 1, and 0.1 cm3 (D2cc, D1cc, and D0.1cc) of the rectum, sigmoid, and bladder, as well as International Commission on Radiation Units and Measurements point doses (DICRU) were computed. Total doses were converted to equivalent doses in 2 Gy by applying the linear-quadratic model (α/β = 3 Gy). Late side effects were prospectively assessed using the Late Effects in Normal Tissues–Subjective, Objective, Management and Analytic score. The following patient groups were defined: Group 1: no side effects (Grade 0); Group 2: side effects (Grade 1–4); Group 3: minor side effects (Grade 0–1); and Group 4: major side effects (Grade 2–4).Results: The median follow-up was 51 months. The overall 5-year actuarial side effect rates were 12% for rectum, 3% for sigmoid, and 23% for bladder. The mean total D2cc were 65 ± 12 Gy for rectum, 62 ± 12 Gy for sigmoid, and 95 ± 22 Gy for bladder. For rectum, statistically significant differences were observed between Groups 1 and 2 in all DVH parameters and DICRU. Between Groups 3 and 4, no difference was observed for D0.1cc. For sigmoid, significant differences were observed for D2cc and D1cc, but not for D0.1cc in all groups. For bladder, significant differences were observed for all DVH parameters only comparing Groups 3 and 4. No differences were observed for DICRU.Conclusions: The parameters D2cc and D1cc have a good predictive value for rectal toxicity. For sigmoid, no prediction could be postulated because of limited data. In bladder, DVH parameters were predictive only for major toxicity."

PCI for NSCLC

The RTOG 0214 reports out in the JCO this week: This was a randomized trial looking at PCI in NSCLC for stage III NSCLC. Unfortunately the trial closed after 356 accrued; their goal was just over 1,000, and the trial was not going to achieve it's objectives. The survival rates at 1year were identical, even with a very significant reduction in the amount of brain metastases (HR 2.5). Of course, one could say that the trial simply didn't have the power to detect the difference, but even with ~350 patients, one would like to at least see a signal of benefit, which was lacking in at least the current analysis.

Looking at the rates of brain mets in the control arm 18%, one must wonder if we could better select those that are likely to develop mets in the future, and run a trial in an enriched cohort with a higher likelihood of disease. This is were I think the future of PCI for NSCLC lies.

In a companion piece, the QOL portion was reported. Not surprisingly there were primarily deteriorations seen in memory and recall - without significant decreases in overall function or global QOL. Nonetheless - this underlines the importance of selecting a group more likely to benefit, in light of known risks.

Link and Abstract from the JCO:

Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non-Small-Cell Lung Cancer: Primary Analysis of Radiation Therapy Oncology Group Study RTOG 0214 [Thoracic Oncology]: "Purpose

This study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non–small-cell lung cancer (LA-NSCLC).

Patients and Methods

Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.

Results

Overall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80).

Conclusion

In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS.

"

JCO: SRS or Surgery +/- WBRT for 1-3 brain mets

JCO this week:

The EORTC publishes a randomized trial looking at the effect of WBRT after surgical or SRS treatment of 1-3 brain mets. Their primary endpoint was time of functional independence, and found no differences in this outcome with the addition of WBRT. Additionally OS was no different, though recurrences were reduced both at the initial site and elsewhere within the brain. The late toxicity was not significantly different between the arms as evaluated by the trial, but the investigators admit that extensive neurocognitive testing was not performed.

The findings were not significantly different than what has been seen in other trials looking at both surgery and SRS. One thing I can't help but observe is that the failures were at least numerically higher in the surgery arm at the primary site. There are certainly reasons why this may be so (and indeed the size of lesions in the surgery cohort were larger), there certainly is no signal that SRS is worse than surgery in appropriately selected patients.

Link and Abstract:

Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study [Neurooncology]: "Purpose

This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases.

Patients and Methods

Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.

Results

Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.

Conclusion

After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.

"

RT and Tamoxifen for DCIS - update of the UK/ANZ trial

In Lancet Oncology this week:

An update of the 2x2 trial of tam and RT for locally excised DCIS is published, confirming the benefit of RT in reducing both non-invasive and invasive disease. Similarly tamoxifen is confirmed to benefit ipisilateral DCIS and contralateral disease, though not ipsilateral invasive recurrence. One of the things that is interesting in this trial, though it is a subgroup analysis, is that the benefit of tamoxifen in ipsilateral recurrences was largely seen in the absence of radiotherapy (see the forest plot on figure 3). Another gratifying conclusion is that there were no increases in contralateral breast events with RT due to carcinogenesis.

Link:

[Articles] Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial: "This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision."

Lancet: Aspirin and reduction in risk of cancer related mortality (Meta-Analysis)

In the Lancet this week there is an interesting article looking at the long term reduction in cancer related mortality in trials looking a daily aspirin use. The investigators performed an individual case meta-analysis of several trials and found a reduction in all cancer related mortality of 0.79 (odd-ratio). This held out to 20 years. The greatest benefit was seen in GI tumors, though it was not confined to them.

Link:

[Articles] Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials: "Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention."

QOL after Bladder Preservation

In the Red Journal:

Prospective evaluations of QOL have been lacking in the literature till recently, which is especially important in a trial of organ preservation. If the organ doesn't function properly post preservation - there is little point, and potentially can adversely affect the patient's quality of life. That is often heard as a counter argument for bladder preservation - "Sure you may preserve the bladder, but it is not going to be functional."

The GETUG has done the field a great favor by prospectively looking at this in their bladder preservation trial. Treatment was similar to the US approach - 45Gy with concurrent CDDP + 5FU, reeval with cysto, with cystectomy recommended for residual tumor, and an 18Gy boost for those without evidence of persistent/recurrent tumor. The majority reported good QOL and bladder function, and importantly with results similar to the cystectomy literature for overall survival.

Link and Abstract

Quality of Life Assessment After Concurrent Chemoradiation for Invasive Bladder Cancer: Results of a Multicenter Prospective Study (GETUG 97-015):

"Purpose: To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial.Patient and Methods: Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment.Results: Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52–79%) of patients. Overall survival was 36% (95% confidence interval, 23–49%) at 8 years for all patients, and 45% (28–61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6–36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months.Conclusions: Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients."

Cardiac Atlas for RT planning

In the Red Journal:

To add to the standardization of contouring: Investigators from Michigan release an atlas for cardiac contouring. Link follows:

Development and Validation of a Heart Atlas to Study Cardiac Exposure to Radiation Following Treatment for Breast Cancer

WBRT after methotrexate for CNS lymphoma

Lancet Oncology:

A randomized trial is reported comparing MTX alone to MTX with WBRT for responders with primary CNS lymphoma. Designed as a non-inferiority trial for progression-free survival, it failed to meet it's endpoint, however, it is observed that the toxicity associated with WBRT in not insignificant. This mirrors the approach taken at Duke currently, of the selective use of WBRT after MTX, with care taken to limit exposure to those at highest risk of toxicity (particularly those >60 years of age). Of course in the non-responders, the worst toxicity is going to be progressive disease without further treatment.

Link

[Articles] High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial: "No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors."

the "Bolla" trial of long term ADT updated

Lancet Oncology:

The "Bolla" trial of Long Term ADT for prostate cancer is updated, with the DFS and OS benefit confirmed out to 10 years. What is also reassuring in this update is that the cardiovascular mortality was not increased with LHRH agonists.

Link:

[Articles] External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study: "In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity."

HPV subtypes for cervical cancer worldwide

Lancet Oncology:

A large report of the prevalence of HPV subtypes causing cervical cancer is published, again confirming HPV 16, 18, 31, and 33 as the primary actors. Interestingly, it also highlights HPV 45, and the prevalence of HPV in cervical adenocarcinomas.

Link:

[Articles] Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study: "To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45."

PET response in treatment of Esophageal cancer

JCO this week:

An interesting retrospective series from Wake Forest examines the potential role of PET in prediction and prognosis in Esophageal cancer. In this series, outcomes of patients treated with trimodality therapy (CT, RT, and surgery) did reasonably well regardless of PET response, but in the definitive CTRT group, PET-CR predicted a large difference in survival and local control. The question now is whether PET can be used to select patients that would benefit from surgery, after completing a course of CTRT, which could potentially spare up to a 1/3 of patient a potentially morbid intervention.

Link and Abstract:

Outcomes of Patients With Esophageal Cancer Staged With [18F]Fluorodeoxyglucose Positron Emission Tomography (FDG-PET): Can Postchemoradiotherapy FDG-PET Predict the Utility of Resection? [Gastrointestinal Cancer]: "Purpose

To determine whether [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) can delineate patients with esophageal cancer who may not benefit from esophagectomy after chemoradiotherapy.
Patients and Methods

We reviewed records of 163 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy with or without resection with curative intent. All patients received surgical evaluation. Initial and postchemoradiotherapy FDG-PET scans and prognostic/treatment variables were analyzed. FDG-PET complete response (PET-CR) after chemoradiotherapy was defined as standardized uptake value ≤ 3.
Results

Eighty-eight patients received trimodality therapy and 75 received chemoradiotherapy. Surgery was deferred primarily due to medical inoperability or unresectable/metastatic disease after chemoradiotherapy. A total of 105 patients were evaluable for postchemoradiotherapy FDG-PET response. Thirty-one percent achieved a PET-CR. PET-CR predicted for improved outcomes for chemoradiotherapy (2-year overall survival, 71% v 11%, P < .01; 2-year freedom from local failure [LFF], 75% v 28%, P < .01), but not trimodality therapy. On multivariate analysis of patients treated with chemoradiotherapy, PET-CR is the strongest independent prognostic variable (survival hazard ratio [HR], 9.82, P < .01; LFF HR, 14.13, P < .01). PET-CR predicted for improved outcomes regardless of histology, although patients with adenocarcinoma achieved a PET-CR less often.
Conclusion

Patients treated with trimodality therapy found no benefit with PET-CR, likely because FDG-PET residual disease was resected. Definitive chemoradiotherapy patients achieving PET-CR had excellent outcomes equivalent to trimodality therapy despite poorer baseline characteristics. Patients who achieve a PET-CR may not benefit from added resection given their excellent outcomes without resection. These results should be validated in a prospective trial of FDG-PET–directed therapy for esophageal cancer.
"

JCO: Gem+RT vs Gem alone in Pancreatic CA

In JCO:

Pancreatic cancer continues to be a difficult tumor to treat, where even the largest recent advances (EGRF inhibition, Gemcitabine) provide very modest benefit at best. Gemcitabine + RT was a subject of some excitement due to the radiosensitizing properties of the drug, but unfortunately in many centers it was found to also sensitize to normal tissue as well. Thus the US approach has been Gem alone, and RT + 5FU or capecitabine if used at all.

The study at hand is at once great in terms of concept by looking at Gem alone vs Gem concurrently with RT , but unfortunately limited by it's scope. As a randomized phase II, little can be concluded, asside from the fact that the toxicities as less than otherwise expected in the concurrent arm. There is not however evidence of a large therapeutic benefit with the approach, thus I feel that, as before, this is a disease in desperate need of a breakthrough.

Link and Abstract

Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study [Gastrointestinal Cancer]: "Purpose

The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer.

Patients and Methods

Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS).

Results

Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%).

Conclusion

Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.

"

Angiosarcoma

Lancet Oncology -

An interesting review article on angiosarcoma in the Lancet Oncology this week: these difficult tumors often involve the radiation oncologist, either as a long term complication of prior therapy (classically breast radiation), or as treatment.

Link

[Review] Angiosarcoma: "Angiosarcomas are rare soft-tissue sarcomas of endothelial cell origin that have a poor prognosis. They can arise anywhere in the body, most commonly presenting as cutaneous disease in elderly white men, involving the head and neck and particularly the scalp. They can be caused by therapeutic radiation or chronic lymphoedema and hence secondary breast angiosarcomas are an important subgroup. Recent work has sought to establish the molecular biology of angiosarcomas and identify specific targets for treatment."

NSABP B-32 - Sentinel Node Study published for OS

In the Lancet Oncology,

Though already common practice, the NSABP B-32 trial randomizing breast cancer patients to sentinel lymph node mapping vs a full axillary dissection is published revealing no difference in any clinical endpoint. This is good news as it already has become standard practice in most US centers. Another thing to keep in mind about this is that there is a 5-15% false negative rate of the procedure, which has clearly not translated into a meaningful difference in outcomes in this trial.

Link:

[Articles] Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial: "Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes."